@article{Anna2022,

title = {Dupilumab-Associated Adverse Events During Treatment of Allergic Diseases. },

author = {Kychygina, Anna; Cassagne, Myriam; Tauber, Marie; Galiacy, Stéphane; Paul, Carle; Fournié, Pierre; Simon, Michel; },

doi = {10.1007/s12016-022-08934-0},

year  = {2022},

date = {2022-01-01},

journal = {Clin Rev Allergy Immunol. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{T2022,

title = {Corneal epithelium in keratoconus underexpresses active NRF2 and a subset of oxidative stress-related genes.},

author = {Lupasco, Tatiana; He, Zhiguo; Cassagne, Myriam; Sagnial, Tomy; Brion, Lise; Fournié, Pierre; Gain, Philippe; Thuret, Gilles; Allouche, Michèle; Malecaze, François; Simon, Michel; Galiacy, Stéphane; },

doi = {10.1371/journal.pone.0273807},

year  = {2022},

date = {2022-01-01},

journal = {PLoS One},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Aurélie2022,

title = {Cold Atmospheric Plasma Jet Treatment Improves Human Keratinocyte Migration and Wound Closure Capacity without Causing Cellular Oxidative Stress. },

author = {Marches, Aurélie; Clement, Emily; Albérola, Géraldine; Rols, Marie-Pierre; Cousty, Sarah; Simon, Michel; Merbahi, Nofel; },

doi = {10.3390/ijms231810650},

year  = {2022},

date = {2022-01-01},

journal = {Int J Mol Sci},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Padhi2022,

title = {IL-22 downregulates peptidylarginine deiminase-1 in human keratinocytes: adding another piece to the IL-22 puzzle in epidermal barrier formation. },

author = {Padhi, Avinash; Srivastava, Ankit; Ramesh, Abarajitha; Ehrström, Marcus; Simon, Michel; Sonkoly, Eniko; Eidsmo, Liv; Bergman, Peter; Lysell, Josefin;},

doi = {10.1016/j.jid.2021.07.155},

year  = {2022},

date = {2022-01-01},

journal = {Invest Dermatol},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mariona2022,

title = {Epidermal 1-O-acylceramides appear with the establishment of the water permeability barrier in mice and are produced by maturating keratinocytes. },

author = {Rabionet, Mariona; Bernard, Pauline; Pichery, Mélanie; Marsching, Christian; Bayerle, Aline; Dworski, Shaalee; Kamani, Mustafa; Chitraju, Chandramohan; Gluchowski, Nina; Gabriel, Katlyn; Asadi, Abolfazl; Ebel, Philipp; Hoekstra, Menno; Dumas, Sabrina; Ntambi, James; Jacobsson, Anders; Willecke, Klaus; Medin, Jeffrey; Jonca, Nathalie; Sandhoff, Roger; },

doi = {10.1002/lipd.12342},

year  = {2022},

date = {2022-01-01},

journal = {Lipids},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Basmanav2022,

title = {Assessment of the Genetic Spectrum of Uncombable Hair Syndrome in a Cohort of 107 Individuals. },

author = {Basmanav, Buket; Cesarato, Nicole; Kumar, Sheetal; Borisov, Oleg; Kokordelis, Pavlos; Ralser, Damian; Wehner, Maria; Axt, Dais; Xiong, Xing; Thiele, Holger; Dolgin, Vadim; Gossmann, Yasmina; Fricker, Nadine; Dewenter Malin, Katharina; Weller, Karsten; Suri, Mohnish; Reichenbach, Herbert; Oji, Vinsenz; Addor, Marie-Claude; Ramirez, Karla; Stewart, Helen; Garcia Bartels, Natalie; Weibel, Lisa; Wagner, Nicola; George, Susannah; Kilic, Arzu; Tantcheva-Poor, Iliana; Stewart, Alison; Dikow, Nicola; Blaumeiser, Bettina; Medvecz, Marta; Blume-Peytavi, Ulrike; Farrant, Paul; Grimalt, Ramon; Bertok, Sara; Bradley, Lisa; Eskin-Schwartz, Marina; Birk Ohad, Samuel; Bygum, Anette; Simon, Michel; Krawitz, Peter; Fischer, Christine; Hamm, Henning; Fritz, Gunter; Betz, Regina; },

doi = {10.1001/jamadermatol.2022.2319},

year  = {2022},

date = {2022-01-01},

journal = {JAMA Dermatol},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cadau2022,

title = {An Inflamed and Infected Reconstructed Human Epidermis to Study Atopic Dermatitis and Skin Care Ingredients. },

author = {Cadau, Sébastien; Gault, Manon; Berthelemy, Nicolas; Hsu, Chiung-Yueh; Danoux, Louis; Pelletier, Nicolas; Goudounèche, Dominique; Pons, Carole; Leprince, Corinne; André-Frei, Valérie; Simon, Michel; Pain, Sabine; },

doi = {10.3390/ijms232112880},

year  = {2022},

date = {2022-01-01},

journal = {Int J Mol Sci. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sara2022,

title = {Cold helium plasma jet does not stimulate collagen remodeling in a 3D human dermal substitute. },

author = {Gouarderes, Sara; Marches, Aurélie; Vicendo, Patricia; Fourquaux, Isabelle; Simon, Michel; Merbahi, Nofel; Gibot, Laure;},

doi = {10.1016/j.bioelechem.2021.107985},

year  = {2022},

date = {2022-01-01},

journal = {Bio electrochemistry},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Elodie2022,

title = {Targeting TGF-β1/miR-21 pathway in keratinocytes reveals protective effects of silymarin on imiquimod-induced psoriasis mouse model.  },

author = {Henriet, Elodie; Abdallah, Florence; Laurent, Yoan; Guimpied, Cyril; Clement, Emily; Simon, Michel; Pichon, Chantal; Baril, Patrick;},

doi = {100175, 2022.},

year  = {2022},

date = {2022-01-01},

journal = {J Invest Dermatol Innov},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Joosten2022,

title = {New developments in the molecular treatment of ichthyosis: review of the literature. },

author = {Joosten, Mandy; Clabbers, Julia; Jonca, Nathalie; Mazereeuw-Hautier, Juliette; Gostyński, Antony;},

doi = {10.1186/s13023-022-02430-6},

year  = {2022},

date = {2022-01-01},

journal = {Orphanet J Rare Dis},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Verena2022,

title = {Revisiting the Roles of Filaggrin in Atopic Dermatitis. },

author = {Moosbrugger-Martinz, Verena; Leprince, Corinne; Méchin, Marie-Claire; Simon, Michel; Blunder, Stefan; Gruber, Robert; Dubrac, Sandrine; },

doi = {10.3390/ijms23105318 },

year  = {2022},

date = {2022-01-01},

journal = {Int J Mol Sci. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lecru2022,

title = {Multiplex Cytokine Analyses in Ear Canals of Dogs Suggest Involvement of IL-8 Chemokine in Atopic Otitis and Otodectic Mange-Preliminary Results. },

author = {Lecru, Line-Alice; Combarros, Daniel; Moog, Fabien; Marinovic, Lukrecija; Kondratjeva, Jevgenija; Amalric, Nicolas; Pressanti, Charline; Cadiergues, Marie-Christine; },

doi = {10.3390/ani12050575},

year  = {2022},

date = {2022-01-01},

journal = {Animals (Basel). },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bruet2022,

title = {Clinical Guidelines for the Use of Antipruritic Drugs in the Control of the Most Frequent Pruritic Skin Diseases in Dogs. },

author = {Bruet, Vincent; Mosca, Marion; Briand, Amaury; Bourdeau, Patrick; Pin, Didier; Cochet-Faivre, Noelle; Cadiergues, Marie-Christine; },

doi = {10.3390/vetsci9040149},

year  = {2022},

date = {2022-01-01},

journal = {Vet Sci. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Audrey2022,

title = {Effectiveness and safety of dupilumab in the treatment of atopic dermatitis in children (6-11 years): data from a French multicentre retrospective cohort in daily practice. },

author = {Lasek, Audrey; Bellon, Nathalie; Mallet, Stéphanie; Puzenat, Eve; Bursztejn, Anne-Claire; Abasq, Claire; Mazereeuw-Hautier, Juliette; Chiaverini, Christine; Hubiche, Thomas; Raison-Peyron, Nadia; Du Thanh, Aurélie; Barbarot, Sébastien; Aubert, Hélène; Reguiai, Ziad; Droitcourt, Catherine; Fievet, Charlotte; Bellissen, Astrid; Bachelerie, Marie; Nosbaum, Audrey; Leymarie, Anne; Armingaud, Philippe; Masson Regnault, Marie; Mahé, Emmanuel; Research Group of the Société Française de Dermatologie Pédiatrique (GR SFDP); Research Group of eczéma atopique (GREAT); },

doi = {10.1111/jdv.18450},

year  = {2022},

date = {2022-01-01},

journal = {J Eur Acad Dermatol Venereol.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Eloi2022,

title = {New Keratoconus Risk Factors: A Cross-Sectional Case-Control Study.},

author = {Debourdeau, Eloi; Planells, Gabriel; Chamard, Chloé; Touboul, David; Villain, Max; Demoly, Pascal; Babeau, Fanny; Fournie, Pierre; Daien, Vincent; },

doi = {10.1155/2022/6605771},

year  = {2022},

date = {2022-01-01},

journal = {J Ophthalmol. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Marie-Noelle2022,

title = {Vocational Guidance for Young Patients with Atopic Dermatitis: A Survey of Physicians' Opinions and Practices. },

author = {Crépy, Marie-Noelle; Bensefa-Colas, Linda; Aubin, François; Simon, Michel; Soria, Angèle; French research group for atopic dermatitis (Groupe de Recherche sur l’Eczéma Atopique) in collaboration with the French Society of Dermatology and Venereology; French Society of Allergology; French Society of Pediatrics and French Society of Occupational Medicine;},

doi = {10.2340/actadv.v102.205},

year  = {2022},

date = {2022-01-01},

journal = {Acta Derm Venereol. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{S2021b,

title = {Cold atmospheric helium plasma does not stimulate dermal collagen remodeling at tissue scale.},

author = {Gouarderes, Sara; Marches, Aurélie; Vicendo, Patricia; Fourquaux, Isabelle; Simon, Michel; Merbahi, Nofel; Gibot, Laure;},

doi = {10.1016/j.bioelechem.2021.107985},

year  = {2021},

date = {2021-10-23},

journal = {Bioelectrochemistry},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{T2021,

title = {Atopic dermatitis: Role of the skin barrier, environment, microbiome, and therapeutic agents.},

author = {Luger, Thomas; Amagai, Masayuki; Dreno, Brigitte; Dagnelie, Marie-Ange; Liao, Wilson; Kabashima, Kenji; Krutmann, J; Proksch, Ehrhardt ; Elias, Peter; Simon, Michel; Simpson, Eric; Schmuth, Matthias;},

doi = {10.1016/j.jdermsci.2021.04.007},

year  = {2021},

date = {2021-05-01},

journal = {Journal of Dermatological Science},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{D2021,

title = {The upper epidermis of atopic dogs is altered at the functional and structural levels. },

author = {Combarros, Daniel; Goudounèche, Dominique; Cadiergues, Marie-Christine; Simon, Michel; },

doi = {10.1111/vde.13024},

year  = {2021},

date = {2021-01-01},

journal = {Vet Dermatol},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{A2021,

title = {Meta-Analysis of Mutations in ALOX12B or ALOXE3 Identified in a Large Cohort of 224 Patients. },

author = {Hotz, Alrun; Kopp, Julia; Bourrat, Emmanuell; Oji, Vinzenz; Komlosi, Katalin; Giehl, Kathrin; Bouadjar, Bajar; Bygum, Anette; Tantcheva-Poor, Iliana; Hellström Pigg, Maritta; Has, Cristina; Yang, Zhou; Irvine, Alan D; Betz C, Regina; Zambruno, Giovana; Tadini, Gianluuca; Süßmuth, Kira; Gruber, Robert; Schmuth, Matthias; Mazereeuw-Hautier, Juliette; Jonca, Nathalie; Guez, Sophie; Brena, Michela; Hernandez-Martin, Angela; Van Den Akker, Peter; Bolling, Maria C.; Hannula-Jouppi, Katarina; Zimmer, Andreas D.; Alter, Svenja; Vahlquist, Anders; Fischer, Judith},

doi = {10.3390/genes12010080},

year  = {2021},

date = {2021-01-01},

journal = {Genes (Basel)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{C2021,

title = {Survey of cytokines on ocular surfaces of atopic dogs by multiplex analysis using two sampling methods - a pilot study. },

author = {Pressanti, Charline; Ravailhe, Élodie; Castellote-Brun, Jessie; Amalric, Nicolas; Lecru, Line-Alice; Kondratjeva, Jevgenija; Moog, Fabien; Combarros, Daniel; Douet, Jean-Yves; Cadiergues, Marie-Christine; },

doi = {10.1111/vde.13010},

year  = {2021},

date = {2021-01-01},

journal = {Vet Dermatol},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tauber2020b,

title = {Latent class analysis categorizes chronic hand eczema patients according to skin barrier impairment.},

author = {Tauber, M and Bérard, E and Lourari, S and Questel, E and Redoules, D and Paul, C and Simon, M},

doi = {10.1111/jdv.16083},

issn = {1468-3083 (Electronic)},

year  = {2020},

date = {2020-07-01},

journal = {Journal of the European Academy of Dermatology and Venereology : JEADV},

volume = {34},

number = {7},

pages = {1529--1535},

abstract = {BACKGROUND: Chronic hand eczema (CHE) is the most common skin disorder affecting the hands. It causes major physical and psychological burden for patients. Classification of CHE remains challenging because of its aetiological and clinical heterogeneity. OBJECTIVES: Using latent class analysis (LCA) on a large categorical data set, our aim was to identify distinct phenotypes in a cohort of unselected CHE patients based upon clinical, genetic, molecular and physical parameters of the affected skin. METHODS: We performed two independent LCA on a cohort of 71 well-characterized patients that initially integrated clinical severity, total immunoglobulin E plasma level, transepidermal water loss, hydration index, interleukin(IL)-8 lesional skin level, Staphylococcus (aureus and epidermidis) colonization, FLG genotype and the expression (mRNA) of genes involved either in the filaggrin degradation and the natural moisturizing factor synthesis, the cornified envelope formation, the tight junctions' structure and the desquamation process, or encoding antimicrobial peptides and chemokines. RESULTS: The first LCA categorized patients into a group displaying high severity of CHE, high skin barrier impairment, high Staphylococcus colonization, high IL-8 skin level and high frequency of mutation in the FLG gene and a second group with opposite characteristics. The second LCA identified two independent groups of patients categorized by their low or high level of skin barrier impairment and corresponding changes in the expression of the related genes. CONCLUSIONS: Our study suggests that the degree of skin barrier dysfunction is the most important parameter to discriminate CHE patients and probably plays a pivotal role in the pathogenesis of the disease whatever the aetiological factors. As far as we know, this is the first study to address this topic using a statistical categorization method without preconception.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Touhouche2020,

title = {Incidence and risk factors for dupilumab associated ocular adverse events: a real-life prospective study.},

author = {Touhouche, A T and Cassagne, M and Bérard, E and Giordano-Labadie, F and Didier, A and Fournié, P and Paul, C and Tauber, M},

doi = {10.1111/jdv.16724},

issn = {1468-3083 (Electronic)},

year  = {2020},

date = {2020-06-01},

journal = {Journal of the European Academy of Dermatology and Venereology : JEADV},

abstract = {BACKGROUND: Dupilumab is approved for use in moderate-to-severe atopic dermatitis (AD) and as an add-on maintenance treatment in patients suffering from severe asthma with type 2 inflammation. Ocular adverse events (OAEs) have been reported with dupilumab almost exclusively in patients treated for AD. OBJECTIVES: The objectives of this study were to describe the incidence and nature of dupilumab-induced OAEs and to assess the potential predisposing factors. PATIENTS AND METHODS: We conducted a prospective, single-centre, real-life study in adult AD patients treated with dupilumab, who were systematically examined by an ophthalmologist before and during treatment. RESULTS: Forty-six patients were included prospectively with a median age of 41.1 years and a median initial SCOring Atopic Dermatitis of 46.0 (IQR: 34.5-55.5). OAEs concerned 34.8% of patients and were mostly of mild to moderate severity. Two patients had to discontinue treatment due to OAE. The majority of patients developed or aggravated dry eye disease, with superficial punctate keratitis (SPK). Six patients developed conjunctivitis. Dupilumab-induced OAEs were associated with the following pre-existing parameters: dry eye disease with SPK (Odds ratio (OR); 6.3 [95% confidence interval (CI): 1.3-31.6]), eyelid eczema (OR: 8.7 [95%CI: 1.8-40.6]), history of food allergy (OR 3.8 (95% CI: 1.002-14,070) and IgE serum leveltextgreater 1000 kU/L (OR:10.6 [CI 95%: 1.2-91.3]). CONCLUSION: Atopic dermatitis patients with eyelid eczema or dry eye disease symptoms may be referred to an ophthalmologist before starting dupilumab to consider initiating preventive eye hydration measures. Further multicentric and translational studies are warranted to better explain OAEs pathophysiology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Thyssen2020b,

title = {Filaggrin Expression and Processing Deficiencies Impair Corneocyte Surface Texture and Stiffness in Mice.},

author = {Thyssen, Jacob P and Jakasa, Ivone and Riethmüller, Christoph and Schön, Michael P and Braun, Andrea and Haftek, Marek and Fallon, Padraic G and Wróblewski, Jacek and Jakubowski, Hieronim and Eckhart, Leopold and Declercq, Wim and Koppes, Sjors and Engebretsen, Kristiane A and Bonefeld, Charlotte and Irvine, Alan D and Keita-Alassane, Sokhna and Simon, Michel and Kawasaki, Hiroshi and Kubo, Akiharu and Amagai, Masayuki and Matsui, Takeshi and Kezic, Sanja},

doi = {10.1016/j.jid.2019.07.716},

issn = {1523-1747 (Electronic)},

year  = {2020},

date = {2020-03-01},

journal = {The Journal of investigative dermatology},

volume = {140},

number = {3},

pages = {615--623.e5},

abstract = {Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp(-/-)), filaggrin (Flg(ft/ft) and Flg(-/-)), filaggrin-hornerin (FlgHrnr(-/-)), and bleomycin hydrolase (Blmh(-/-)) were investigated. Sasp(-/-) and Flg(-/-) were on the hairless mouse background. Atomic force microscopy was used to determine elastic modulus and dermal texture index. Corneocytes of each neonatal as well as hairless adult knockout mouse exhibited an increased number of protrusions and decreased elastic modulus. In these mice, NMFs were reduced except for Sasp(-/-). Dermal texture index was inversely correlated with NMFs and elastic modulus. Our findings demonstrate that any filaggrin-NMF axis deficiency can affect corneocyte mechanical properties in mice and likely in humans. Differences in NMFs and corneocyte surface texture between neonatal and adult as well as hairless and hairy mice emphasize the need for carefully selecting the most appropriate animal models for studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tauber2020,

title = {Positive change in hand care habits using therapeutic patient education in chronic hand eczema.},

author = {Tauber, Marie and Lourari, Siham and Bérard, Emilie and Questel, Emmanuel and Redoules, Daniel and Giordano-Labadie, Françoise and Simon, Michel and Carle, Paul},

doi = {10.1111/cod.13390},

issn = {1600-0536 (Electronic)},

year  = {2020},

date = {2020-01-01},

journal = {Contact dermatitis},

volume = {82},

number = {1},

pages = {10--17},

institution = {Therapeutic Education Group (GET) of the French Society of Dermatology (SFD)},

abstract = {BACKGROUND: Chronic hand eczema (CHE) is a major burden for patients. Maintenance treatment involves prevention measures limiting detrimental behaviour and aggravating factors. OBJECTIVE: To evaluate the effect of a standardised care program including therapeutic patient education (TPE) on hand care behaviours, clinical severity, quality of life, and work productivity. METHODS: A single-centre study was conducted prospectively. Together with the prescription of a topical steroid, patients participated in individual TPE sessions. Evaluations were performed initially and repeated three months after the therapeutic intervention. They included a structured analysis of hand care behaviours, the assessment of the mTLSS (modified Total Lesion Symptom Score), DLQI (Dermatology Life Quality Index), and WPAI (Work Productivity and Activity Impairment). RESULTS: Seventy-one patients were included (30 men, 42.3%). Three months after completion of the standardised care program, hand care behaviours such as hand washing and rinsing, hand drying, wearing protective gloves, using moisturizing creams, and following specific treatments and recommendations for CHE improved significantly in the 58 patients who completed the study and were associated with a significant improvement in the mTLSS, DLQI, and WPAI scores. CONCLUSIONS: TPE helps patients change their hand care behaviours and adopt skin protection measures, and may improve CHE severity, quality of life, and work productivity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mechin2020,

title = {Deimination and Peptidylarginine Deiminases in Skin Physiology and Diseases.},

author = {Méchin, Marie-Claire and Takahara, Hidenari and Simon, Michel},

doi = {10.3390/ijms21020566},

issn = {1422-0067 (Electronic)},

year  = {2020},

date = {2020-01-01},

journal = {International journal of molecular sciences},

volume = {21},

number = {2},

abstract = {Deimination, also known as citrullination, corresponds to the conversion of the amino acid arginine, within a peptide sequence, into the non-standard amino acid citrulline. This post-translational modification is catalyzed by a family of calcium-dependent enzymes called peptidylarginine deiminases (PADs). Deimination is implicated in a growing number of physiological processes (innate and adaptive immunity, gene regulation, embryonic development, etc.) and concerns several human diseases (rheumatoid arthritis, neurodegenerative diseases, female infertility, cancer, etc.). Here, we update the involvement of PADs in both the homeostasis of skin and skin diseases. We particularly focus on keratinocyte differentiation and the epidermal barrier function, and on hair follicles. Indeed, alteration of PAD activity in the hair shaft is responsible for two hair disorders, the uncombable hair syndrome and a particular form of inflammatory scarring alopecia, mainly affecting women of African ancestry.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cau2019,

title = {Peptidylarginine Deiminase Inhibitor Cl-Amidine Attenuates Cornification and Interferes with the Regulation of Autophagy in Reconstructed Human Epidermis.},

author = {Cau, Laura and Takahara, Hidenari and Thompson, Paul R and Serre, Guy and Méchin, Marie-Claire and Simon, Michel},

doi = {10.1016/j.jid.2019.02.026},

issn = {1523-1747 (Electronic)},

year  = {2019},

date = {2019-09-01},

journal = {The Journal of investigative dermatology},

volume = {139},

number = {9},

pages = {1889--1897.e4},

abstract = {Deimination, a post-translational modification catalyzed by a family of enzymes called peptidylarginine deiminases (PADs), is the conversion of arginine into citrulline residues in a protein. Deimination has been associated with numerous physiological and pathological processes. Our aim was to study its implication in the homeostasis of human epidermis, where three PADs are expressed, namely PAD1, 2, and 3. Three-dimensional reconstructed human epidermis (RHEs) were treated for 2 days with increased concentrations (0-800 $mu$M) of Cl-amidine, a specific PAD inhibitor. Cl-amidine treatments inhibited deimination in a dose-dependent manner and were not cytotoxic for keratinocytes. At 800 $mu$M , Cl-amidine was shown to reduce deimination by half, alter keratinocyte differentiation, decrease the number of corneocyte layers, significantly increase the number of transitional cells, induce clustering of mitochondria and of heterogeneous vesicles in the cytoplasm of granular keratinocytes, and upregulate the expression of autophagy proteins, including LC3-II, sestrin-2, and p62/SQSTM1. LC3 and PADs were further shown to partially co-localize in the upper epidermis. These results demonstrated that Cl-amidine treatments slow down cornification and alter autophagy in the granular layer. They suggest that PAD1 and/or PAD3 play a role in the constitutive epidermal autophagy process that appears as an important step in cornification.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Reynier2019,

title = {The Actin-Based Motor Myosin Vb Is Crucial to Maintain Epidermal Barrier Integrity.},

author = {Reynier, Marie and Allart, Sophie and Goudounèche, Dominique and Moga, Alain and Serre, Guy and Simon, Michel and Leprince, Corinne},

doi = {10.1016/j.jid.2018.12.021},

issn = {1523-1747 (Electronic)},

year  = {2019},

date = {2019-07-01},

journal = {The Journal of investigative dermatology},

volume = {139},

number = {7},

pages = {1430--1438},

abstract = {Myosin Vb (Myo5b) is an unconventional myosin involved in the actin-dependent transport and tethering of intracellular organelles. In the epidermis, granular keratinocytes accumulate cytoplasmic lamellar bodies (LBs), secretory vesicles released at the junction with the stratum corneum that participate actively in the maintenance of the epidermal barrier. We have previously demonstrated that LB biogenesis is controlled by the Rab11a guanosine triphosphate hydrolase, known for its ability to recruit the Myo5b motor. In order to better characterize the molecular pathway that controls LB trafficking, we analyzed the role of F-actin and Myo5b in the epidermis. We demonstrated that LB distribution in granular keratinocytes was dependent on a dynamic F-actin cytoskeleton. Myo5b was shown to be highly expressed in granular keratinocytes and associated with corneodesmosin-loaded LB. In reconstructed human epidermis, Myo5b silencing led to epidermal barrier defects associated with structural alterations of the stratum corneum and a reduced pool of LB showing signs of disordered maturation. Myo5b depletion also disturbed the expression and distribution of both LB cargoes and junctional components, such as claudin-1, which demonstrates its action on both LB trafficking and junctional complex composition. Together, our data reveal the essential role of Myo5b in maintaining the epidermal barrier integrity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tauber2019,

title = {Effect of dupilumab on atopic manifestations in patients treated for atopic dermatitis in real-life practice.},

author = {Tauber, M and Apoil, P A and Richet, C and Laurent, J and De Bonnecaze, G and Mouchon, E and Cassagne, M and Marguery, M C and Hegazy, S and Konstantinou, M P and Severino, M and Uthurriague, C and Giordano-Labadie, F and Didier, A and Paul, C},

doi = {10.1111/bjd.17629},

issn = {1365-2133 (Electronic)},

year  = {2019},

date = {2019-06-01},

booktitle = {The British journal of dermatology},

volume = {180},

number = {6},

pages = {1551--1552},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{,

title = {The Amino-Terminal Part of Human FLG2 Is a Component of Cornified Envelopes.},

author = {Albérola, Géraldine and Schröder, Jens-Michael and Froment, Carine and Simon, Michel},

doi = {10.1016/j.jid.2018.11.022},

issn = {1523-1747 (Electronic)},

year  = {2019},

date = {2019-06-01},

booktitle = {The Journal of investigative dermatology},

journal = {The Journal of investigative dermatology},

volume = {139},

number = {6},

pages = {1395--1397},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mazereeuw-Hautier2019,

title = {Management of congenital ichthyoses: European guidelines of care, part one.},

author = {Mazereeuw-Hautier, J and Vahlquist, A and Traupe, H and Bygum, A and Amaro, C and Aldwin, M and Audouze, A and Bodemer, C and Bourrat, E and Diociaiuti, A and Dolenc-Voljc, M and Dreyfus, I and El Hachem, M and Fischer, J and Gaanemo, A and Gouveia, C and Gruber, R and Hadj-Rabia, S and Hohl, D and Jonca, N and Ezzedine, K and Maier, D and Malhotra, R and Rodriguez, M and Ott, H and Paige, D G and Pietrzak, A and Poot, F and Schmuth, M and Sitek, J C and Steijlen, P and Wehr, G and Moreen, M and O'Toole, E A and Oji, V and Hernandez-Martin, A},

doi = {10.1111/bjd.17203},

issn = {1365-2133 (Electronic)},

year  = {2019},

date = {2019-02-01},

journal = {The British journal of dermatology},

volume = {180},

number = {2},

pages = {272--281},

abstract = {These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016 and a consensus on the discussions. They summarize evidence and expert-based recommendations and are intended to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part one, covering topical therapies, systemic therapies, psychosocial management, communicating the diagnosis and genetic counselling.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Malki2019,

title = {Variant PADI3 in Central Centrifugal Cicatricial Alopecia.},

author = {Malki, Liron and Sarig, Ofer and Romano, Maria-Teresa and Méchin, Marie-Claire and Peled, Alon and Pavlovsky, Mor and Warshauer, Emily and Samuelov, Liat and Uwakwe, Laura and Briskin, Valeria and Mohamad, Janan and Gat, Andrea and Isakov, Ofer and Rabinowitz, Tom and Shomron, Noam and Adir, Noam and Simon, Michel and McMichael, Amy and Dlova, Ncoza C and Betz, Regina C and Sprecher, Eli},

doi = {10.1056/NEJMoa1816614},

issn = {1533-4406 (Electronic)},

year  = {2019},

date = {2019-02-01},

journal = {The New England journal of medicine},

volume = {380},

number = {9},

pages = {833--841},

abstract = {BACKGROUND: Central centrifugal cicatricial alopecia (CCCA) is the most common form of scarring alopecia among women of African ancestry. The disease is occasionally observed to affect women in families in a manner that suggests an autosomal dominant trait and usually manifests clinically after intense hair grooming. We sought to determine whether there exists a genetic basis of CCCA and, if so, what it is. METHODS: We used exome sequencing in a group of women with alopecia (discovery set), compared the results with those in a public repository, and applied other filtering criteria to identify candidate genes. We then performed direct sequencing to identify disease-associated DNA variations and RNA sequencing, protein modeling, immunofluorescence staining, immunoblotting, and an enzymatic assay to evaluate the consequences of potential etiologic mutations. We used a replication set that consisted of women with CCCA to confirm the data obtained with the discovery set. RESULTS: In the discovery set, which included 16 patients, we identified one splice site and three heterozygous missense mutations in PADI3 in 5 patients (31%). (The approximate prevalence of the disease is up to 5.6%.) PADI3 encodes peptidyl arginine deiminase, type III (PADI3), an enzyme that post-translationally modifies other proteins that are essential to hair-shaft formation. All three CCCA-associated missense mutations in PADI3 affect highly conserved residues and are predicted to be pathogenic; protein modeling suggests that they result in protein misfolding. These mutations were found to result in reduced PADI3 expression, abnormal intracellular localization of the protein, and decreased enzymatic activity - findings that support their pathogenicity. Immunofluorescence staining showed decreased expression of PADI3 in biopsy samples of scalp skin obtained from patients with CCCA. We then directly sequenced PADI3 in an additional 42 patients (replication set) and observed genetic variants in 9 of them. A post hoc analysis of the combined data sets showed that the prevalence of PADI3 mutation was higher among patients with CCCA than in a control cohort of women of African ancestry (P = 0.002 by the chi-square test; P = 0.006 by Fisher's exact test; and after adjustment for relatedness of persons, P = 0.03 and P = 0.04, respectively). CONCLUSIONS: Mutations in PADI3, which encodes a protein that is essential to proper hair-shaft formation, were associated with CCCA. (Funded by the Ram Family Foundation and others.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pin2019,

title = {Refined Immunochemical Characterization in Healthy Dog Skin of the Epidermal Cornification Proteins, Filaggrin, and Corneodesmosin.},

author = {Pin, Didier and Pendaries, Valérie and Keita Alassane, Sokhna and Froment, Carine and Amalric, Nicolas and Cadiergues, Marie-Christine and Serre, Guy and Haftek, Marek and Vidémont, Emilie and Simon, Michel},

doi = {10.1369/0022155418798807},

issn = {1551-5044 (Electronic)},

year  = {2019},

date = {2019-02-01},

journal = {The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society},

volume = {67},

number = {2},

pages = {85--97},

abstract = {Filaggrin (FLG) and corneodesmosin (CDSN) are two key proteins of the human epidermis. FLG loss-of-function mutations are the strongest genetic risk factors for human atopic dermatitis. Studies of the epidermal distribution of canine FLG and CDSN are limited. Our aim was to better characterize the distribution of FLG and CDSN in canine skin. Using immunohistochemistry on beagle skin, we screened a series of monoclonal antibodies (mAbs) specific for human FLG and CDSN. The cross-reactive mAbs were further used using immunoelectron microscopy and Western blotting. The structure of canine CDSN and FLG was determined using publicly available databases. In the epidermis, four anti-FLG mAbs stained keratohyalin granules in the granular keratinocytes and corneocyte matrix of the lower cornified layer. In urea-extracts of dog epidermis, several bands corresponding to proFLG and FLG monomers were detected. One anti-CDSN mAb stained the cytoplasm of granular keratinocytes and cells of both the inner root sheath and medulla of hair follicles. Dog CDSN was located in lamellar bodies, in the extracellular parts of desmosomes and in corneodesmosomes. A protein of 52 kDa was immunodetected. Genomic DNA analysis revealed that the amino acid sequence and structure of canine and human CDSN were highly similar.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zingkou2019,

title = {Activography reveals aberrant proteolysis in desquamating diseases of differing backgrounds.},

author = {Zingkou, Eleni and Pampalakis, Georgios and Kiritsi, Dimitra and Valari, Manthoula and Jonca, Nathalie and Sotiropoulou, Georgia},

doi = {10.1111/exd.13832},

issn = {1600-0625 (Electronic)},

year  = {2019},

date = {2019-01-01},

booktitle = {Experimental dermatology},

journal = {Experimental dermatology},

volume = {28},

number = {1},

pages = {86--89},

abstract = {The role of epidermal proteolysis in overdesquamation was revealed in Netherton syndrome, a rare ichthyosis due to genetic deficiency of the LEKTI inhibitor of serine proteases. Recently, we developed activography, a new histochemical method, to spatially localize and semiquantitatively assess proteolytic activities using activity-based probes. Activography provides specificity and versatility compared to in situ zymography, the only available method to determine enzymatic activities in tissue biopsies. Here, activography was validated in skin biopsies obtained from an array of distinct disorders and compared with in situ zymography. Activography provides a methodological advancement due to its simplicity and specificity and can be readily adapted as a routine diagnostic assay. Interestingly, the levels of epidermal proteolysis correlated with the degree of desquamation independent of skin pathology. Thus, deregulated epidermal proteolysis likely represents a universal mechanism underlying aberrant desquamation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cau2018,

title = {Peptidylarginine deiminases and deiminated proteins at the epidermal barrier.},

author = {Cau, Laura and Méchin, Marie-Claire and Simon, Michel},

doi = {10.1111/exd.13684},

issn = {1600-0625 (Electronic)},

year  = {2018},

date = {2018-08-01},

journal = {Experimental dermatology},

volume = {27},

number = {8},

pages = {852--858},

abstract = {Deimination or citrullination is a post-translational modification catalysed by a family of calcium-dependent enzymes called peptidylarginine deiminases (PADs). It corresponds to the transformation of arginine residues within a peptide sequence into citrulline residues. Deimination induces a decreased net charge of targeted proteins; therefore, it alters their folding and changes intra- and intermolecular ionic interactions. Deimination is involved in several physiological processes (inflammation, gene regulation, etc.) and human diseases (rheumatoid arthritis, neurodegenerative diseases, cancer, etc.). Here, we describe the PADs expressed in the epidermis and their known substrates, focusing on their role in the epidermal barrier function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hsu2018,

title = {Stabilization of microtubules restores barrier function after cytokine-induced defects in reconstructed human epidermis.},

author = {Hsu, Chiung-Yueh and Lecland, Nicolas and Pendaries, Valérie and Viodé, Cécile and Redoulès, Daniel and Paul, Carle and Merdes, Andreas and Simon, Michel and Bierkamp, Christiane},

doi = {10.1016/j.jdermsci.2018.04.008},

issn = {1873-569X (Electronic)},

year  = {2018},

date = {2018-07-01},

journal = {Journal of dermatological science},

volume = {91},

number = {1},

pages = {87--96},

abstract = {BACKGROUND: A variety of human skin disorders is characterized by defects in the epidermal barrier, leading to dehydration, itchiness, and rashes. Previously published literature suggests that microtubule stabilization at the cortex of differentiating keratinocytes is necessary for the formation of the epidermal barrier. OBJECTIVES: We tested whether stabilization of microtubules with paclitaxel or epothilone B can repair barrier defects that were experimentally induced in three-dimensional culture models of epidermis. METHODS: We established two models of defective epidermis in vitro, using three-dimensional cultures of primary human keratinocytes on filter supports: immature reconstructed human epidermis (RHE), and RHE that was compromised by treatment with inflammatory cytokines, the latter mimicking defects seen in atopic dermatitis. RESULTS: Both paclitaxel and epothilone B promoted keratinocyte differentiation, accumulation of junctional proteins at the cell cortex, and the early appearance of lamellar bodies in immature RHE, whereas destabilization of microtubules by nocodazole had the reverse effect. Moreover, stabilization of microtubules rescued the barrier after cytokine treatment. The rescued barrier function correlated with the restoration of filaggrin and loricrin protein levels, the cortical accumulation of junctional proteins (E-cadherin, $beta$-catenin, and claudin-1), and with the secretion of lamellar bodies. CONCLUSIONS: Our data suggest that the microtubule network is important for the formation of the epidermis, and that stabilization of microtubules promotes barrier formation. Microtubule stabilization may support regeneration of damaged skin, by restoring or improving the barrier.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zaafouri2018,

title = {Transcriptomic Analysis of Two Cdsn-Deficient Mice Shows Gene Signatures Biologically Relevant for Peeling Skin Disease.},

author = {Zaafouri, Sarra and Pichery, Mélanie and Huchenq, Anne and Valentin, Frederic and Oji, Vinzenz and Mazereeuw-Hautier, Juliette and Serre, Guy and Jonca, Nathalie},

doi = {10.1016/j.jid.2017.12.020},

issn = {1523-1747 (Electronic)},

year  = {2018},

date = {2018-06-01},

booktitle = {The Journal of investigative dermatology},

journal = {The journal of investigative dermatology},

volume = {138},

number = {6},

pages = {1431--1435},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Onnis2018,

title = {KLICK syndrome: an unusual phenotype.},

author = {Onnis, G and Bourrat, E and Jonca, N and Dreyfus, I and Severino-Freire, M and Pichery, M and Fischer, J and Mazereeuw-Hautier, J},

doi = {10.1111/bjd.16318},

issn = {1365-2133 (Electronic)},

year  = {2018},

date = {2018-06-01},

booktitle = {The British journal of dermatology},

journal = {British journal of dermatology},

volume = {178},

number = {6},

pages = {1445--1446},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cau2017,

title = {Lowering relative humidity level increases epidermal protein deimination and drives human filaggrin breakdown.},

author = {Cau, Laura and Pendaries, Valérie and Lhuillier, Emeline and Thompson, Paul R and Serre, Guy and Takahara, Hidenari and Méchin, Marie-Claire and Simon, Michel},

doi = {10.1016/j.jdermsci.2017.02.280},

issn = {1873-569X (Electronic)},

year  = {2017},

date = {2017-05-01},

journal = {Journal of dermatological science},

volume = {86},

number = {2},

pages = {106--113},

abstract = {BACKGROUND: Deimination (also known as citrullination), the conversion of arginine in a protein to citrulline, is catalyzed by a family of enzymes called peptidylarginine deiminases (PADs). Three PADs are expressed in the epidermis, one of their targets being filaggrin. Filaggrin plays a central role in atopic dermatitis and is a key protein for the epidermal barrier. It aggregates keratins and is cross-linked to cornified envelopes. Following its deimination, it is totally degraded to release free amino acids, contributing to the natural moisturizing factor (NMF). The mechanisms controlling this multistep catabolism in human are unknown. OBJECTIVE: To test whether external humidity plays a role, and investigate the molecular mechanisms involved. METHODS: Specimens of reconstructed human epidermis (RHEs) produced in humid or dry conditions (textgreater95% or 30-50% relative humidity) were compared. RESULTS: RHEs produced in the dry condition presented structural changes, including a thicker stratum corneum and a larger amount of keratohyalin granules. The transepidermal water loss and the stratum corneum pH were decreased whereas the quantity of NMF was greater. This highly suggested that filaggrin proteolysis was up-regulated. The expression/activity of the proteases involved in filaggrin breakdown did not increase while PAD1 expression and the deimination rate of proteins, including filaggrin, were drastically enhanced. Partial inhibition of PADs with Cl-amidine reversed the effect of dryness on filaggrin breakdown. CONCLUSION: These results demonstrate the importance of external humidity in the control of human filaggrin metabolism, and suggest that deimination plays a major role in this regulation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pichery2017,

title = {PNPLA1 defects in patients with autosomal recessive congenital ichthyosis and KO mice sustain PNPLA1 irreplaceable function in epidermal omega-O-acylceramide synthesis and skin permeability barrier.},

author = {Pichery, Mélanie and Huchenq, Anne and Sandhoff, Roger and Severino-Freire, Maella and Zaafouri, Sarra and Opálka, Lukáš, and Levade, Thierry and Soldan, Vanessa and Bertrand-Michel, Justine and Lhuillier, Emeline and Serre, Guy and Maruani, Annabel and Mazereeuw-Hautier, Juliette and Jonca, Nathalie},

doi = {10.1093/hmg/ddx079},

issn = {1460-2083 (Electronic)},

year  = {2017},

date = {2017-05-01},

journal = {Human molecular genetics},

volume = {26},

number = {10},

pages = {1787--1800},

abstract = {Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of monogenic genodermatoses that encompasses non-syndromic disorders of keratinization. The pathophysiology of ARCI has been linked to a disturbance in epidermal lipid metabolism that impaired the stratum corneum function, leading to permeability barrier defects. Functional characterization of some genes involved in ARCI contributed to the identification of molecular actors involved in epidermal lipid synthesis, transport or processing. Recently, PNPLA1 has been identified as a gene causing ARCI. While other members of PNPLA family are key elements in lipid metabolism, the function of PNPLA1 remained unclear. We identified 5 novel PNPLA1 mutations in ARCI patients, mainly localized in the putative active enzymatic domain of PNPLA1. To investigate Pnpla1 biological role, we analysed Pnpla1-deficient mice. KO mice died soon after birth from severe epidermal permeability defects. Pnpla1-deficient skin presented an important impairment in the composition and organization of the epidermal lipids. Quantification of epidermal ceramide species highlighted a blockade in the production of $ømega$-O-acylceramides with a concomitant accumulation of their precursors in the KO. The virtually loss of $ømega$-O-acylceramides in the stratum corneum was linked to a defective lipid coverage of the resistant pericellular shell encapsulating corneocytes, the so-called cornified envelope, and most probably disorganized the extracellular lipid matrix. Finally, these defects in $ømega$-O-acylceramides synthesis and cornified envelope formation were also evidenced in the stratum corneum from PNPLA1-mutated patients. Overall, our data support that PNPLA1/Pnpla1 is a key player in the formation of $ømega$-O-acylceramide, a crucial process for the epidermal permeability barrier function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hsu2017,

title = {Deimination of Human Hornerin Enhances its Processing by Calpain-1 and its Cross-Linking by Transglutaminases.},

author = {Hsu, Chiung-Yueh and Gasc, Géraldine and Raymond, Anne-Aurélie and Burlet-Schiltz, Odile and Takahara, Hidenari and Serre, Guy and Méchin, Marie-Claire and Simon, Michel},

doi = {10.1016/j.jid.2016.09.030},

issn = {1523-1747 (Electronic)},

year  = {2017},

date = {2017-02-01},

journal = {The Journal of investigative dermatology},

volume = {137},

number = {2},

pages = {422--429},

abstract = {Hornerin (HRNR) shares numerous features with filaggrin, a key contributor to the epidermal barrier functions. The two proteins display a related structural organization, are expressed by the granular keratinocytes as a large precursor processed by proteolysis, and are cross-linked to the cornified cell envelopes. Two main steps in the metabolism of filaggrin are its deimination and calpain-1 cleavage. Here, using ion-exchange chromatography and two-dimensional gel electrophoresis of human epidermis extracts, we determined that HRNR is deiminated in vivo. Accordingly, cornified envelopes, purified from plantar and abdominal human skin, were shown to contain deiminated proteins. A recombinant form of HRNR (HRNR(His)) deiminated in vitro was shown to be a better substrate for transglutaminases 1 and 3 than the unmodified form. Our data also indicated that calpain-1 may be involved in the proteolytic processing of HRNR, because calpain-1 was co-located with HRNR in the cytoplasm of granular keratinocytes. Using Western blotting and mass spectrometry analysis, HRNR(His) was shown to be cleaved by calpain-1 in vitro, its deimination enhancing its proteolysis. In HRNR full sequence, four calpain-1 cleavage sites were identified. Altogether, these data allowed a new role to be deciphered for deimination during cornification and provided further characterization of HRNR metabolism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{UBasmanav2016,

title = {Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome.},

author = {Ü Basmanav, F Buket and Cau, Laura and Tafazzoli, Aylar and Méchin, Marie-Claire and Wolf, Sabrina and Romano, Maria Teresa and Valentin, Frederic and Wiegmann, Henning and Huchenq, Anne and Kandil, Rima and Garcia Bartels, Natalie and Kilic, Arzu and George, Susannah and Ralser, Damian J and Bergner, Stefan and Ferguson, David J P and Oprisoreanu, Ana-Maria and Wehner, Maria and Thiele, Holger and Altmüller, Janine and Nürnberg, Peter and Swan, Daniel and Houniet, Darren and Büchner, Aline and Weibel, Lisa and Wagner, Nicola and Grimalt, Ramon and Bygum, Anette and Serre, Guy and Blume-Peytavi, Ulrike and Sprecher, Eli and Schoch, Susanne and Oji, Vinzenz and Hamm, Henning and Farrant, Paul and Simon, Michel and Betz, Regina C},

doi = {10.1016/j.ajhg.2016.10.004},

issn = {1537-6605 (Electronic)},

year  = {2016},

date = {2016-12-01},

journal = {American journal of human genetics},

volume = {99},

number = {6},

pages = {1292--1304},

abstract = {Uncombable hair syndrome (UHS), also known as "spun glass hair syndrome," "pili trianguli et canaliculi," or "cheveux incoiffables" is a rare anomaly of the hair shaft that occurs in children and improves with age. UHS is characterized by dry, frizzy, spangly, and often fair hair that is resistant to being combed flat. Until now, both simplex and familial UHS-affected case subjects with autosomal-dominant as well as -recessive inheritance have been reported. However, none of these case subjects were linked to a molecular genetic cause. Here, we report the identification of UHS-causative mutations located in the three genes PADI3 (peptidylarginine deiminase 3), TGM3 (transglutaminase 3), and TCHH (trichohyalin) in a total of 11 children. All of these individuals carry homozygous or compound heterozygous mutations in one of these three genes, indicating an autosomal-recessive inheritance pattern in the majority of UHS case subjects. The two enzymes PADI3 and TGM3, responsible for posttranslational protein modifications, and their target structural protein TCHH are all involved in hair shaft formation. Elucidation of the molecular outcomes of the disease-causing mutations by cell culture experiments and tridimensional protein models demonstrated clear differences in the structural organization and activity of mutant and wild-type proteins. Scanning electron microscopy observations revealed morphological alterations in hair coat of Padi3 knockout mice. All together, these findings elucidate the molecular genetic causes of UHS and shed light on its pathophysiology and hair physiology in general.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Li2016,

title = {Counterregulation between thymic stromal lymphopoietin- and IL-23-driven immune axes shapes skin inflammation in mice with epidermal barrier defects.},

author = {Li, Jiagui and Leyva-Castillo, Juan Manuel and Hener, Pierre and Eisenmann, Aurelie and Zaafouri, Sarra and Jonca, Nathalie and Serre, Guy and Birling, Marie-Christine and Li, Mei},

doi = {10.1016/j.jaci.2016.01.013},

issn = {1097-6825 (Electronic)},

year  = {2016},

date = {2016-07-01},

journal = {The Journal of allergy and clinical immunology},

volume = {138},

number = {1},

pages = {150--161.e13},

abstract = {BACKGROUND: Epidermal barrier dysfunction has been recognized as a critical factor in the initiation and exacerbation of skin inflammation, particularly in patients with atopic dermatitis (AD) and AD-like congenital disorders, including peeling skin syndrome type B. However, inflammatory responses developed in barrier-defective skin, as well as the underlying mechanisms, remained incompletely understood. OBJECTIVE: We aimed to decipher inflammatory axes and the cytokine network in mouse skin on breakdown of epidermal stratum corneum barrier. METHODS: We generated Cdsn(iep-/-) mice with corneodesmosin ablation in keratinocytes selectively in an inducible manner. We characterized inflammatory responses and cytokine expression by using histology, immunohistochemistry, ELISA, and quantitative PCR. We combined mouse genetic tools, antibody-mediated neutralization, signal-blocking reagents, and topical antibiotic treatment to explore the inflammatory axes. RESULTS: We show that on breakdown of the epidermal stratum corneum barrier, type 2 and type 17 inflammatory responses are developed simultaneously, driven by thymic stromal lymphopoietin (TSLP) and IL-23, respectively. Importantly, we reveal a counterregulation between these 2 inflammatory axes. Furthermore, we show that protease-activated receptor 2 signaling is involved in mediating the TSLP/type 2 axis, whereas skin bacteria are engaged in induction of the IL-23/type 17 axis. Moreover, we find that IL-1$beta$ is induced in skin of Cdsn(iep-/-) mice and that blockade of IL-1 signaling suppresses both TSLP and IL-23 expression and ameliorates skin inflammation. CONCLUSION: The inflammatory phenotype in barrier-defective skin is shaped by counterregulation between the TSLP/type 2 and IL-23/type 17 axes. Targeting IL-1 signaling could be a promising therapeutic option for controlling skin inflammation in patients with peeling skin syndrome type B and other diseases related to epidermal barrier dysfunction, including AD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hotz2016,

title = {Expanding the Clinical and Genetic Spectrum of KRT1, KRT2 and KRT10 Mutations in Keratinopathic Ichthyosis.},

author = {Hotz, Alrun and Oji, Vinzenz and Bourrat, Emmanuelle and Jonca, Nathalie and Mazereeuw-Hautier, Juliette and Betz, Regina C and Blume-Peytavi, Ulrike and Stieler, Karola and Morice-Picard, Fanny and Schönbuchner, Ines and Markus, Susanne and Schlipf, Nina and Fischer, Judith},

doi = {10.2340/00015555-2299},

issn = {1651-2057 (Electronic)},

year  = {2016},

date = {2016-05-01},

journal = {Acta dermato-venereologica},

volume = {96},

number = {4},

pages = {473--478},

abstract = {Twenty-six families with keratinopathic ichthyoses (epidermolytic ichthyosis, superficial epidermolytic ichthyosis or congenital reticular ichthyosiform erythroderma) were studied. Epidermolytic ichthyosis is caused by mutations in the genes KRT1 or KRT10, mutations in the gene KRT2 lead to superficial epidermolytic ichthyosis, and congenital reticular ichthyosiform erythroderma is caused by frameshift mutations in the genes KRT10 or KRT1, which lead to the phenomenon of revertant mosaicism. In this study mutations were found in KRT1, KRT2 and KRT10, including 8 mutations that are novel pathogenic variants. We report here the first case of a patient with congenital reticular ichthyosiform erythroderma carrying a mutation in KRT10 that does not lead to an arginine-rich reading frame. Novel clinical features found in patients with congenital reticular ichthyosiform erythroderma are described, such as mental retardation, spasticity, facial dysmorphisms, symblepharon and malposition of the 4th toe.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Maier2016,

title = {Novel mutation in NIPAL4 in a Romanian family with autosomal recessive congenital ichthyosis.},

author = {Maier, D and Mazereeuw-Hautier, J and Tilinca, M and Cosgarea, R and Jonca, N},

doi = {10.1111/ced.12740},

issn = {1365-2230 (Electronic)},

year  = {2016},

date = {2016-04-01},

journal = {Clinical and experimental dermatology},

volume = {41},

number = {3},

pages = {279--282},

abstract = {Autosomal recessive congenital ichthyosis (ARCI), a severe and highly clinically heterogeneous group of mendelian disorders of cornification, is the result of mutations in at least nine genes regulating the epidermal barrier functionality. NIPAL4 is the second most frequently mutated ARCI gene. We report two adult patients from a nonconsanguineous family of Romanian origin, who had lamellar ichthyosis. A positive in situ transglutaminase 1 activity assay excluded a putative TGM1 mutation. NIPAL4 sequencing revealed in both patients a new homozygous missense mutation, c.403AtextgreaterC, affecting a highly conserved amino acid (p. Ser135Arg) and predicted to be deleterious according to in silico analysis. In addition to the ARCI features, the patients had caries and partial edentation. Although delay in dental treatment led to caries progression and extraction of secondary teeth, this finding raises the possibility of a deficiency in enamel mineralization due to NIPAL4 dysfunction as an Mg(2+) transporter. Evaluating new patients with ARCI provides fruitful clinical and molecular findings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tauber2016,

title = {Staphylococcus aureus density on lesional and nonlesional skin is strongly associated with disease severity in atopic dermatitis.},

author = {Tauber, Marie and Balica, Stefana and Hsu, Chiung-Yueh and Jean-Decoster, Catherine and Lauze, Christophe and Redoules, Daniel and Viodé, Cécile and Schmitt, Anne-Marie and Serre, Guy and Simon, Michel and Paul, Carle F},

doi = {10.1016/j.jaci.2015.07.052},

issn = {1097-6825 (Electronic)},

year  = {2016},

date = {2016-04-01},

booktitle = {The Journal of allergy and clinical immunology},

journal = {The journal of allergy and clinical immunology},

volume = {137},

number = {4},

pages = {1272--1274.e3},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Malaisse2016,

title = {Hyaluronan Does Not Regulate Human Epidermal Keratinocyte Proliferation and Differentiation.},

author = {Malaisse, Jérémy and Pendaries, Val{é}rie and Hontoir, Fanny and De Glas, Valérie and Van Vlaender, Daniel and Simon, Michel and {Lambert de Rouvroit}, Catherine and Poumay, Yves and Flamion, Bruno},

doi = {10.1074/jbc.M115.661348},

issn = {1083-351X (Electronic)},

year  = {2016},

date = {2016-03-01},

journal = {The Journal of biological chemistry},

volume = {291},

number = {12},

pages = {6347--6358},

abstract = {Hyaluronan (HA) is synthesized by three HA synthases (HAS1, HAS2, and HAS3) and secreted in the extracellular matrix. In human skin, large amounts of HA are found in the dermis. HA is also synthesized by keratinocytes in the epidermis, although its epidermal functions are not clearly identified yet. To investigate HA functions, we studied the effects of HA depletion on human keratinocyte physiology within in vitro reconstructed human epidermis. Inhibition of HA synthesis with 4-methylumbelliferone (4MU) did not modify the expression profile of the epidermal differentiation markers involucrin, keratin 10, and filaggrin during tissue reconstruction. In contrast, when keratinocytes were incubated with 4MU, cell proliferation was decreased. In an attempt to rescue the proliferation function, HA samples of various mean molecular masses were added to keratinocyte cultures treated with 4MU. These samples were unable to rescue the initial proliferation rate. Furthermore, treatments with HA-specific hyaluronidase, although removing almost all HA from keratinocyte cultures, did not alter the differentiation or proliferation processes. The differences between 4MU and hyaluronidase effects did not result from differences in intracellular HA, sulfated glycosaminoglycan concentration, apoptosis, or levels of HA receptors, all of which remained unchanged. Similarly, knockdown of UDP-glucose 6-dehydrogenase (UGDH) using lentiviral shRNA effectively decreased HA production but did not affect proliferation rate. Overall, these data suggest that HA levels in the human epidermis are not directly correlated with keratinocyte proliferation and differentiation and that incubation of cells with 4MU cannot equate with HA removal.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mechin2016,

title = {Acefylline activates filaggrin deimination by peptidylarginine deiminases in the upper epidermis.},

author = {Méchin, Marie-Claire and Cau, Laura and Galliano, Marie-Florence and Daunes-Marion, Sylvie and Poigny, Stéphane and Vidaluc, Jean-Louis and Bessou-Touya, Sandrine and Takahara, Hidenari and Serre, Guy and Duplan, Hélène and Simon, Michel},

doi = {10.1016/j.jdermsci.2015.11.006},

issn = {1873-569X (Electronic)},

year  = {2016},

date = {2016-02-01},

journal = {Journal of dermatological science},

volume = {81},

number = {2},

pages = {101--106},

abstract = {BACKGROUND: Peptidylarginine deiminases (PADs) catalyze deimination (or citrullination), a calcium-dependent post-translational modification involved in several physiological processes and human diseases, such as rheumatoid arthritis and cancer. Deimination of filaggrin (FLG) by PAD1 and PAD3 during the last steps of keratinocyte differentiation is a crucial event for the epidermis function and homeostasis. This allows the complete degradation of FLG, leading to the production of free amino acids and their derivatives that are essential for epidermal photoprotection and moisturizing of the stratum corneum. OBJECTIVE: To increase the flux of this catabolic pathway, we searched for activators of PADs. METHODS: A large chemical library was screened first in silico and then by using an automated assay based on an indirect colorimetric measurement of recombinant human PAD activity. Potential activators were then confirmed using a recombinant human FLG as a substrate, and secondly after topical application at the surface of three-dimensional reconstructed human epidermis. RESULTS: The data obtained after the library screening pointed to xanthine derivatives as potential PAD activators. Among seven xanthine derivatives tested at 50-300$mu$M, caffeine, theobromine and acefylline proved to be the most potent enhancers of in vitro deimination of FLG by PAD1 and PAD3. After topical application of a gel formulation containing 3% acefylline at the surface of reconstructed epidermis, immunoblotting analysis showed an increase in the total amount of deiminated proteins, and confocal microscopy showed an enhanced deimination in the stratum corneum. This demonstrated the activation of PADs in living cells. CONCLUSION: As a PAD activator, acefylline will be useful to study the role of deimination and could be proposed to increase or correct the hydration of the cornified layers of the epidermis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{LeLamer2015,

title = {Defects of corneocyte structural proteins and epidermal barrier in atopic dermatitis.},

author = {Le Lamer, Marina and Pellerin, Laurence and Reynier, Marie and Cau, Laura and Pendaries, Valérie and Leprince, Corinne and Méchin, Marie-Claire and Serre, Guy and Paul, Carle and Simon, Michel},

doi = {10.1515/hsz-2015-0141},

issn = {1437-4315 (Electronic)},

year  = {2015},

date = {2015-11-01},

journal = {Biological chemistry},

volume = {396},

number = {11},

pages = {1163--1179},

abstract = {The main function of the epidermis is to establish a vital multifunctional barrier between the body and its external environment. A defective epidermal barrier is one of the key features of atopic dermatitis (AD), a chronic and relapsing inflammatory skin disorder that affects up to 20% of children and 2-3% of adults and often precedes the development of allergic rhinitis and asthma. This review summarizes recent discoveries on the origin of the skin barrier alterations in AD at the structural protein level, including hereditary and acquired components. The consequences of the epidermal barrier alteration on our current understanding of the pathogenesis of AD, and its possible implications on the treatment of patients, are discussed here.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Valentin2015,

title = {Increased expression of caspase-1 and interleukin-18 in peeling skin disease, and a novel mutation of corneodesmosin.},

author = {Valentin, Frederic and Oji, Vinzenz and Hausser, Ingrid and Liebau, Eva and Tarinski, Tatjana and Metze, Dieter and Breitkreutz, Dirk and Traupe, Heiko and Jonca, Nathalie and Terheyden, Patrick},

doi = {10.2340/00015555-2142},

issn = {1651-2057 (Electronic)},

year  = {2015},

date = {2015-11-01},

journal = {Acta dermato-venereologica},

volume = {95},

number = {8},

pages = {1019--1021},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pendaries2015,

title = {In a three-dimensional reconstructed human epidermis filaggrin-2 is essential for proper cornification.},

author = {Pendaries, V and Le Lamer, M and Cau, L and Hansmann, B and Malaisse, J and Kezic, S and Serre, G and Simon, M},

doi = {10.1038/cddis.2015.29},

issn = {2041-4889 (Electronic)},

year  = {2015},

date = {2015-02-01},

journal = {Cell death & disease},

volume = {6},

number = {2},

pages = {e1656},

abstract = {Atopic dermatitis is a chronic inflammatory skin disease with defects in the epidermal barrier. In a cohort of African-American children, a FLG2 nonsense mutation has been associated with the disease. In the epidermis of European patients, the expression of filaggrin-2, the filaggrin-related protein encoded by FLG2, is decreased. To describe the function of filaggrin-2 and evaluate the impact of its deficiency, its expression was downregulated using lentivirus-mediated shRNA interference in a three-dimensional reconstructed human epidermis (RHE) model. This resulted in parakeratosis and a compact stratum corneum, presence of abnormal vesicles inside the corneocytes, increased pH and reduced amounts of free amino acids at the RHE surface, leading to increased sensitivity to UVB radiations. The expression of differentiation markers was slightly modified. However, we observed reduced proteolytic processing of corneodesmosin, hornerin and filaggrin in parallel with reduced amounts of caspase-14 and bleomycin hydrolase. Our data demonstrated that filaggrin-2 is important for a proper cornification and a functional stratum corneum. Its downregulation in atopic patients may be involved in the disease-associated epidermis impairment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pendaries2014,

title = {Knockdown of filaggrin in a three-dimensional reconstructed human epidermis impairs keratinocyte differentiation.},

author = {Pendaries, Valérie and Malaisse, Jeremy and Pellerin, Laurence and Le Lamer, Marina and Nachat, Rachida and Kezic, Sanja and Schmitt, Anne-Marie and Paul, Carle and Poumay, Yves and Serre, Guy and Simon, Michel},

doi = {10.1038/jid.2014.259},

issn = {1523-1747 (Electronic)},

year  = {2014},

date = {2014-12-01},

journal = {The Journal of investigative dermatology},

volume = {134},

number = {12},

pages = {2938--2946},

abstract = {Atopic dermatitis is a chronic inflammatory skin disorder characterized by defects in the epidermal barrier and keratinocyte differentiation. The expression of filaggrin, a protein thought to have a major role in the function of the epidermis, is downregulated. However, the impact of this deficiency on keratinocytes is not really known. This was investigated using lentivirus-mediated small-hairpin RNA interference in a three-dimensional reconstructed human epidermis (RHE) model, in the absence of other cell types than keratinocytes. Similar to what is known for atopic skin, the experimental filaggrin downregulation resulted in hypogranulosis, a disturbed corneocyte intracellular matrix, reduced amounts of natural moisturizing factor components, increased permeability and UV-B sensitivity of the RHE, and impaired keratinocyte differentiation at the messenger RNA and protein levels. In particular, the amounts of two filaggrin-related proteins and one protease involved in the degradation of filaggrin, bleomycin hydrolase, were lower. In addition, caspase-14 activation was reduced. These results demonstrate the importance of filaggrin for the stratum corneum properties/functions. They indicate that filaggrin downregulation in the epidermis of atopic patients, either acquired or innate, may be directly responsible for some of the disease-related alterations in the epidermal differentiation program and epidermal barrier function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pellerin2014,

title = {Bleomycin hydrolase downregulation in lesional skin of adult atopic dermatitis patients is independent of FLG gene mutations.},

author = {Pellerin, Laurence and Paul, Carle and Schmitt, Anne-Marie and Serre, Guy and Simon, Michel},

doi = {10.1016/j.jaci.2014.07.056},

issn = {1097-6825 (Electronic)},

year  = {2014},

date = {2014-12-01},

journal = {The Journal of allergy and clinical immunology},

volume = {134},

number = {6},

pages = {1459--1461.e7},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bergboer2014,

title = {Analysis of protein-protein interaction between late cornified envelope proteins and corneodesmosin.},

author = {Bergboer, Judith G M and Dulak, Maria G and van Vlijmen-Willems, Ivonne M J J and Jonca, Nathalie and van Wijk, Erwin and Hendriks, Wiljan J A J and Zeeuwen, Patrick L J M and Schalkwijk, Joost},

doi = {10.1111/exd.12524},

issn = {1600-0625 (Electronic)},

year  = {2014},

date = {2014-10-01},

booktitle = {Experimental dermatology},

journal = {The journal of investigative dermatology},

volume = {23},

number = {10},

pages = {769--771},

abstract = {Deletion of two members of the late cornified envelope (LCE) family, LCE3B and LCE3C (LCE3C_LCE3B-del), has been identified as risk factor for psoriasis with a possible role in skin barrier function. Moreover, genetic interaction between LCE3C_LCE3B-del and HLA-C*06, located in the psoriasis susceptibility regions 4 and 1 (PSORS4 and 1), has been reported in several populations. Because of high linkage disequilibrium between the PSORS1 genes HLA-C*06 and corneodesmosin (CDSN), both genes are potentially involved in psoriasis. As corneodesmosin and LCE proteins are both constituents of the stratum corneum, we investigated potential direct protein-protein interactions between six LCE proteins and two corneodesmosin sequence variants. Partial colocalization of LCE2 and CDSN was observed in normal and psoriasis skin using immunofluorescence microscopy. Co-expression of eCFP-LCE and mRFP-CDSN proteins in COS-1 cells and human adult keratinocytes, and GST pull-down results did not provide evidence for direct interactions between LCE proteins and CDSN variants.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fredonnet2014,

title = {Topographical and nano-mechanical characterization of native corneocytes using atomic force microscopy.},

author = {Fredonnet, Julie and Gasc, Géraldine and Serre, Guy and Séverac, Childérick and Simon, Michel},

doi = {10.1016/j.jdermsci.2014.04.009},

issn = {1873-569X (Electronic)},

year  = {2014},

date = {2014-07-01},

booktitle = {Journal of dermatological science},

journal = {Journal of dermatological science},

volume = {75},

number = {1},

pages = {63--65},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Leclerc2014,

title = {Mice deficient for the epidermal dermokine $beta$ and $gamma$ isoforms display transient cornification defects.},

author = {Leclerc, Emilie A and Huchenq, Anne and Kezic, Sanja and Serre, Guy and Jonca, Nathalie},

doi = {10.1242/jcs.144808},

issn = {1477-9137 (Electronic)},

year  = {2014},

date = {2014-07-01},

journal = {Journal of cell science},

volume = {127},

number = {Pt 13},

pages = {2862--2872},

abstract = {Expression of the human dermokine gene (DMKN) leads to the production of four dermokine isoform families. The secreted $alpha$, $beta$ and $gamma$ isoforms have an epidermis-restricted expression pattern, with Dmkn $beta$ and $gamma$ being specifically expressed by the granular keratinocytes. The $delta$ isoforms are intracellular and ubiquitous. Here, we performed an in-depth characterization of Dmkn expression in mouse skin and found an expression pattern that was less complex than in humans. In particular, mRNA coding for the $delta$ family were absent. Homozygous mice null for the Dmkn $beta$ and $gamma$ isoforms had no obvious phenotype but only a temporary scaly skin during the first week of life. The pups null for the Dmkn $beta$ and $gamma$ isoforms had smaller keratohyalin granules and their cornified envelopes were more sensitive to mechanical stress. At the molecular level, amounts of profilaggrin and filaggrin monomers were reduced whereas amino acid components of the natural moisturizing factor were increased. In addition, the electrophoretic mobility of involucrin was modified, suggesting post-translational modifications. Finally, the mice null for the Dmkn $beta$ and $gamma$ isoforms strongly overexpressed Dmkn $alpha$. These data are evocative of compensatory mechanisms relevant to the temporary phenotype. Overall, we improved the knowledge of Dmkn expression in mouse and highlighted a role for Dmkn $beta$ and $gamma$ in cornification.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hayez2014,

title = {High TMEM45A expression is correlated to epidermal keratinization.},

author = {Hayez, Aurélie and Malaisse, Jérémy and Roegiers, Edith and Reynier, Marie and Renard, Chantal and Haftek, Marek and Geenen, Vincent and Serre, Guy and Simon, Michel and de Rouvroit, Catherine Lambert and Michiels, Carine and Poumay, Yves},

doi = {10.1111/exd.12403},

issn = {1600-0625 (Electronic)},

year  = {2014},

date = {2014-05-01},

journal = {Experimental dermatology},

volume = {23},

number = {5},

pages = {339--344},

abstract = {TMEM45A (DERP7, DNAPTP4 or FLJ10134) gene, belonging to the TMEM family encoding predicted transmembrane proteins, is highly expressed in epidermal keratinocytes. To investigate the potential involvement of TMEM45A during the differentiation and keratinization processes, its expression has been characterized in normal human keratinocytes and the protein subcellular localization has been studied in this cell type, both in vitro and in vivo. TMEM45A expression is upregulated with differentiation, either induced by cultured keratinocyte confluence or enhanced Ca(2+) concentration in medium. In vivo, TMEM45A mRNA and protein are mostly found in the granular layer of the epidermis. TMEM45A expression is linked to keratinization, as accumulation of the protein is detected in native and reconstructed epidermis as well as in thymic Hassal bodies, but not in non-keratinized stratified epithelia. At the subcellular level, co-detection with ER and Golgi markers reveals that TM protein 45A is associated with the Golgi apparatus and more specifically with the trans-Golgi/trans-Golgi network in vitro and in granular layer in vivo. The protein is neither related to lysosomes nor transported within corneodesmosin-containing lamellar bodies. These data demonstrate a strong correlation between TMEM45A expression and epidermal keratinization, indicating the relevance of this gene in this process.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kezic2014,

title = {Skin barrier in atopic dermatitis.},

author = {Kezic, Sanja and Novak, Natalija and Jakasa, Ivone and Jungersted, Jackob M and Simon, Michel and Brandner, Johanna M and Middelkamp-Hup, Maritza A and Weidinger, Stephan},

doi = {10.2741/4225},

issn = {1093-4715 (Electronic)},

year  = {2014},

date = {2014-01-01},

journal = {Frontiers in bioscience (Landmark edition)},

volume = {19},

pages = {542--556},

abstract = {The skin represents the largest organ of the body and provides a vital interface between the body and the environment. Hereditary and acquired alterations of structural proteins and lipids of the stratum corneum and epidermal tight junctions leading to a diminished skin barrier function are major causative factors for a number of skin diseases, in particular atopic dermatitis (AD). This review summarizes current knowledge on the role of the skin barrier in AD with regard to pathogenesis and treatment, on the relationship between skin barrier abnormalities and immune aberrations, and on potential therapies aimed at repair of the skin barrier. Furthermore recent advances in the genetics of AD will be addressed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mallet2013,

title = {Identification of the first nonsense CDSN mutation with expression of a truncated protein causing peeling skin syndrome type B.},

author = {Mallet, A and Kypriotou, M and George, K and Leclerc, E and Rivero, D and Mazereeuw-Hautier, J and Serre, G and Huber, M and Jonca, N and Hohl, D},

doi = {10.1111/bjd.12593},

issn = {1365-2133 (Electronic)},

year  = {2013},

date = {2013-12-01},

journal = {The British journal of dermatology},

volume = {169},

number = {6},

pages = {1322--1325},

abstract = {BACKGROUND: Peeling skin disease (PSD), a generalized inflammatory form of peeling skin syndrome, is caused by autosomal recessive nonsense mutations in the corneodesmosin gene (CDSN). OBJECTIVES: To investigate a novel mutation in CDSN. METHODS: A 50-year-old white woman showed widespread peeling with erythema and elevated serum IgE. DNA sequencing, immunohistochemistry, Western blot and real-time polymerase chain reaction analyses of skin biopsies were performed in order to study the genetics and to characterize the molecular profile of the disease. RESULTS: Histology showed hyperkeratosis and acanthosis of the epidermis, and inflammatory infiltrates in the dermis. DNA sequencing revealed a homozygous mutation leading to a premature termination codon in CDSN: p.Gly142*. Protein analyses showed reduced expression of a 16-kDa corneodesmosin mutant in the upper epidermal layers, whereas the full-length protein was absent. CONCLUSIONS: These results are interesting regarding the genotype-phenotype correlations in diseases caused by CDSN mutations. The PSD-causing CDSN mutations identified heretofore result in total corneodesmosin loss, suggesting that PSD is due to full corneodesmosin deficiency. Here, we show for the first time that a mutant corneodesmosin can be stably expressed in some patients with PSD, and that this truncated protein is very probably nonfunctional.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pellerin2013,

title = {Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin.},

author = {Pellerin, Laurence and Henry, Julie and Hsu, Chiung-Yueh and Balica, Stéfana and Jean-Decoster, Catherine and Méchin, Marie-Claire and Hansmann, Britta and Rodriguez, Elke and Weindinger, Stefan and Schmitt, Anne-Marie and Serre, Guy and Paul, Carle and Simon, Michel},

doi = {10.1016/j.jaci.2012.12.1566},

issn = {1097-6825 (Electronic)},

year  = {2013},

date = {2013-04-01},

journal = {The Journal of allergy and clinical immunology},

volume = {131},

number = {4},

pages = {1094--1102},

abstract = {BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a disturbed epidermal barrier. In a subset of patients, this is explained by nonsense mutations in the gene encoding filaggrin (FLG). OBJECTIVES: We sought to evaluate the respective role of FLG mutations and proinflammatory cytokines and to assess the expression of FLG, hornerin (HRNR), and FLG2, 2 FLG-like proteins, which are involved in epidermal barrier functions, in normal skin and both lesional and nonlesional skin of patients with AD. METHODS: An FLG-genotyped cohort of 73 adults with AD and 73 aged-matched control subjects was analyzed by using immunohistochemistry and immunoblotting. Normal primary human keratinocytes were differentiated in either the absence or presence of IL-4, IL-13, and IL-25. RESULTS: Compared with control subjects, FLG, HRNR, and FLG2 were detected at significantly lower levels in the skin of patients with AD, irrespective of their FLG genotype. The reduction was greater in lesional compared with nonlesional skin. In addition, the proFLG/FLG ratio was found to be higher in the skin of wild-type patients than in control subjects. Cytokine treatment of keratinocytes induced a dramatic reduction in FLG, FLG2, and HRNR expression both at the mRNA and protein levels. CONCLUSION: The stratum corneum of lesional but also clinically unaffected skin of adults with AD is abnormal, with reduced expression of FLG and FLG-like proteins. In addition to nonsense mutations, proinflammatory cytokines and some defects in the proFLG processing can contribute to the FLG downregulation. Our study suggests that skin inflammation reduces the expression of FLG-like proteins, contributing to the AD-related epidermal barrier dysfunction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DeKoning2012,

title = {Expression profile of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins during skin barrier repair.},

author = {de Koning, H D and van den Bogaard, E H and Bergboer, J G M and Kamsteeg, M and van Vlijmen-Willems, I M J J and Hitomi, K and Henry, J and Simon, M and Takashita, N and Ishida-Yamamoto, A and Schalkwijk, J and Zeeuwen, P L J M},

doi = {10.1111/j.1365-2133.2012.10885.x},

issn = {1365-2133 (Electronic)},

year  = {2012},

date = {2012-06-01},

journal = {The British journal of dermatology},

volume = {166},

number = {6},

pages = {1245--1254},

abstract = {BACKGROUND: Recent studies have emphasized the importance of heritable and acquired skin barrier abnormalities in common inflammatory diseases such as psoriasis and atopic dermatitis (AD). To date, no comprehensive studies on the effect of experimental barrier disruption on cornified envelope protein expression have been performed. OBJECTIVES: To analyse the effect of experimental skin barrier disruption on the expression of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins. METHODS: We examined mRNA (day 1, 3 and 7) and protein (day 1, 2, 4 and 9) expression levels of structural proteins and regulatory molecules after sodium dodecyl sulphate (SDS) application on normal skin, and tape stripping of uninvolved epidermis of patients with psoriasis and AD and healthy controls. RESULTS: Upon tape stripping, several structural molecules were significantly downregulated (at the mRNA level as well as the protein level), including LCE5A, LCE2B, FLG, FLG2 and LOR, whereas others were upregulated: IVL, SPRR1, SPRR2, HRNR and most notably LCE3A. The epidermal crosslinking enzymes TGM1, TGM3 and TGM5 were all upregulated, whereas proteases involved in the desquamation process (CTSV, KLK5 and KLK7) were downregulated or unaffected. Most results were similar in SDS-instigated irritant contact dermatitis. There was no significant difference in response between normal epidermis and nonlesional skin of patients with psoriasis and AD. CONCLUSIONS: Skin barrier disruption induces a temporary barrier repair response composed of increased expression of several cornification-related proteins, and decreased expression of some structural and desquamation-related proteins.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lagarrigue2012,

title = {In vivo quantification of epidermis pigmentation and dermis papilla density with reflectance confocal microscopy: variations with age and skin phototype.},

author = {Lagarrigue, Sophie Garrido and George, Jerome and Questel, Emmanuel and Lauze, Christophe and Meyer, Nicolas and Lagarde, Jean-Michel and Simon, Michel and Schmitt, Anne-Marie and Serre, Guy and Paul, Carle},

doi = {10.1111/j.1600-0625.2012.01451.x},

issn = {1600-0625 (Electronic)},

year  = {2012},

date = {2012-04-01},

journal = {Experimental dermatology},

volume = {21},

number = {4},

pages = {281--286},

abstract = {Reflectance confocal microscopy (RCM) may help to quantify variations of skin pigmentation induced by different stimuli such as UV radiation or therapeutic intervention. The objective of our work was to identify RCM parameters able to quantify in vivo dermis papilla density and epidermis pigmentation potentially applicable in clinical studies. The study included 111 healthy female volunteers with phototypes I-VI. Photo-exposed and photo-protected anatomical sites were imaged. The effect of age was also assessed. Four epidermis components were specifically investigated: stratum corneum, stratum spinosum, basal epidermal layer and dermo-epidermal junction. Laser power, diameter of corneocytes and upper spinous keratinocytes, brightness of upper spinous and interpapillary spinous keratinocytes, number of dermal papillae and papillary contrast were systematically assessed. Papillary contrast measured at the dermo-epidermal junction appeared to be a reliable marker of epidermis pigmentation and showed a strong correlation with skin pigmentation assessed clinically using the Fitzpatrick's classification. Brightness of upper spinous and interpapillary spinous keratinocytes was not influenced by the skin phototype. The number of dermal papillae was significantly lower in subjects with phototypes I-II as compared with darker skin subjects. A dramatic reduction in the number of dermal papillae was noticed with age, particularly in subjects with fair skin. The method presented here provides a new in vivo investigation tool for quantification of dermis papilla density and epidermal pigmentation. Papillary contrast measured at the dermo-epidermal junction may be selected as a marker of skin pigmentation for evaluation in clinical studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mazereeuw-Hautier2012,

title = {Factors influencing quality of life in patients with inherited ichthyosis: a qualitative study in adults using focus groups.},

author = {Mazereeuw-Hautier, J and Dreyfus, I and Barbarot, S and Serrentino, L and Bourdon-Lanoy, E and Ezzedine, K and Maza, A and Aujoulat, I and Le Rhun, A},

doi = {10.1111/j.1365-2133.2011.10701.x},

issn = {1365-2133 (Electronic)},

year  = {2012},

date = {2012-03-01},

journal = {The British journal of dermatology},

volume = {166},

number = {3},

pages = {646--648},

abstract = {BACKGROUND: There is limited information regarding quality of life in patients with inherited ichthyosis. OBJECTIVES: To identify factors influencing quality of life in patients with inherited ichthyosis. METHODS: The study used focus groups and involved adult patients suffering from inherited ichthyosis from three French hospital centres. Group discussions were conducted by two facilitators and were continued until data saturation was reached. The verbatim transcripts were analysed independently by two investigators. Categories considered as key factors in the modulation of quality of life were negotiated until agreement was obtained. RESULTS: Data saturation was reached after the fifth group. A total of 25 patients affected by various forms of ichthyosis attended these focus groups. The identified factors influencing quality of life were related to physical health, daily life, relations with others or oneself. However, together with difficulties related to ichthyosis, patients also underlined some positive aspects of the disease and described specific measures used to improve their quality of life. CONCLUSIONS: This is the first study investigating the different factors that could impact quality of life in patients with ichthyosis. This provides an essential framework from which physicians can develop strategies to improve patient care and quality of life and to develop a specific quality of life questionnaire.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Henry2012,

title = {Update on the epidermal differentiation complex.},

author = {Henry, Julie and Toulza, Eve and Hsu, Chiung-Yueh and Pellerin, Laurence and Balica, Stefana and Mazereeuw-Hautier, Juliette and Paul, Carle and Serre, Guy and Jonca, Nathalie and Simon, Michel},

doi = {10.2741/4001},

issn = {1093-4715 (Electronic)},

year  = {2012},

date = {2012-01-01},

journal = {Frontiers in bioscience (Landmark edition)},

volume = {17},

pages = {1517--1532},

abstract = {On human chromosome 1q21, a 2-Mb region called the epidermal differentiation complex comprises many genes encoding structural and regulatory proteins that are of crucial importance for keratinocyte differentiation and stratum corneum properties. Apart from those for involucrin and loricrin, most of the genes are organized in four families: the genes encoding EF-hand calcium-binding proteins of the S100A family, the genes encoding the small proline rich proteins (SPRRs) and the late cornified envelope (LCE) proteins, two families of cornified cell envelope components, and the genes encoding the S100-fused type proteins (SFTPs). This review focuses on the SPRRs, LCE proteins and SFTPs. It describes their structures, their specific functions and, when known, the mechanisms involved in the regulation of their expression. It also highlights their possible involvement in skin diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bodemer2011,

title = {Short- and medium-term efficacy of specific hydrotherapy in inherited ichthyosis.},

author = {Bodemer, C and Bourrat, E and Mazereeuw-Hautier, J and Boralevi, F and Barbarot, S and Bessis, D and Blanchet-Bardon, C and Bourdon-Lanoy, E and Stalder, J-F and Ribet, V and Guerrero, D and Sibaud, V},

doi = {10.1111/j.1365-2133.2011.10510.x},

issn = {1365-2133 (Electronic)},

year  = {2011},

date = {2011-11-01},

journal = {The British journal of dermatology},

volume = {165},

number = {5},

pages = {1087--1094},

abstract = {BACKGROUND: Management of inherited ichthyoses is symptomatic. Despite treatment, skin symptoms have a major impact on patients' quality of life (QoL). OBJECTIVES: To assess the short- and medium-term efficacy of hydrotherapy on QoL and clinical symptoms of patients with inherited ichthyosis. METHODS: In this 9-month prospective, open-label, multicentre study, 20 children and 24 adults with ichthyosis were enrolled in several French reference and competence centres, 2 months before undergoing a 3-week treatment with specific hydrotherapeutic management at Avène Hydrotherapy Centre. At baseline (2 months before hydrotherapy), beginning (D0) and end of hydrotherapy (D18), and 3 and 6 months later at the reference and competence centres, patients self-assessed QoL using the Dermatology Life Quality Index (DLQI) or its paediatric version (Children's DLQI), and investigators evaluated ichthyosis severity using a specific clinical ichthyosis score. RESULTS: The DLQI scores were significantly improved not only at the end of the hydrotherapy treatment (-56% vs. baseline; mean ± SD 3textperiodcentered59 ± 4textperiodcentered30 at D18 vs. 8textperiodcentered35 ± 5textperiodcentered71 at D0; P textless 0textperiodcentered0001), but also at 3 months (-28% vs. baseline; P = 0textperiodcentered01) and 6 months after hydrotherapy (-26% vs. baseline; mean ± SD 5textperiodcentered21 ± 5textperiodcentered11 vs. 6textperiodcentered89 ± 5textperiodcentered38; P = 0textperiodcentered03) (primary criterion). Clinical symptoms were also significantly improved at all post-treatment visits, with a decrease of the mean clinical ichthyosis score by -38% between D0 and D18, by -30% at 3 months and by -31% at 6 months vs. baseline. CONCLUSIONS: A 3-week treatment at Avène Hydrotherapy Centre provided significant and persisting improvement of QoL and clinical symptoms in patients with inherited ichthyoses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mazereeuw-Hautier2011,

title = {A novel mutation in CDSN causes peeling skin disease in a patient from Morocco.},

author = {Mazereeuw-Hautier, J and Leclerc, E A and Simon, M and Serre, G and Jonca, N},

doi = {10.1111/j.1365-2133.2011.10529.x},

issn = {1365-2133 (Electronic)},

year  = {2011},

date = {2011-11-01},

booktitle = {The British journal of dermatology},

journal = {British journal of dermatology},

volume = {165},

number = {5},

pages = {1152--1155},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hsu2011,

title = {Deimination of human filaggrin-2 promotes its proteolysis by calpain 1.},

author = {Hsu, Chiung-Yueh and Henry, Julie and Raymond, Anne-Aurélie and Méchin, Marie-Claire and Pendaries, Valérie and Nassar, Dany and Hansmann, Britta and Balica, Stéfana and Burlet-Schiltz, Odile and Schmitt, Anne-Marie and Takahara, Hidenari and Paul, Carle and Serre, Guy and Simon, Michel},

doi = {10.1074/jbc.M110.197400},

issn = {1083-351X (Electronic)},

year  = {2011},

date = {2011-07-01},

journal = {The Journal of biological chemistry},

volume = {286},

number = {26},

pages = {23222--23233},

abstract = {Filaggrin-2 (FLG2), a member of the S100-fused type protein family, shares numerous features with filaggrin (FLG), a key protein implicated in the epidermal barrier functions. Both display a related structural organization, an identical pattern of expression and localization in human epidermis, and proteolytic processing of a large precursor. Here, we tested whether FLG2 was a substrate of calpain 1, a calcium-dependent protease directly involved in FLG catabolism. In addition, deimination being critical for FLG degradation, we analyzed whether FLG2 deimination interfered with its proteolytic processing. With this aim, we first produced a recombinant form of FLG2 corresponding to subunits B7 to B10 fused to a COOH-terminal His tag. Incubation with calpain 1 in the presence of calcium induced a rapid degradation of the recombinant protein and the production of several peptides, as shown by Coomassie Blue-stained gels and Western blotting with anti-FLG2 or anti-His antibodies. MALDI-TOF mass spectrometry confirmed this result and further evidenced the production of non-immunoreactive smaller peptides. The degradation was not observed when a calpain 1-specific inhibitor was added. The calpain cleavage sites identified by Edman degradation were regularly present in the B-type repeats of FLG2. Moreover, immunohistochemical analysis of normal human skin revealed colocalization of FLG2 and calpain 1 in the upper epidermis. Finally, the FLG2 deiminated by human peptidylarginine deiminases was shown to be more susceptible to calpain 1 than the unmodified protein. Altogether, these data demonstrate that calpain 1 is essential for the proteolytic processing of FLG2 and that deimination accelerates this process.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jonca2011,

title = {Protease sensitivity of corneodesmosin variants encoded by the six more common CDSN haplotypes.},

author = {Jonca, Nathalie and Caubet, Cécile and Leclerc, Emilie A and Guerrin, Marina and Simon, Michel and Serre, Guy},

doi = {10.1038/jid.2011.7},

issn = {1523-1747 (Electronic)},

year  = {2011},

date = {2011-06-01},

booktitle = {The Journal of investigative dermatology},

journal = {The journal of investigative dermatology},

volume = {131},

number = {6},

pages = {1381--1384},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Henry2011,

title = {Hornerin is a component of the epidermal cornified cell envelopes.},

author = {Henry, Julie and Hsu, Chiung-Yueh and Haftek, Marek and Nachat, Rachida and de Koning, Heleen D and Gardinal-Galera, Isabelle and Hitomi, Kiyotaka and Balica, Stéfana and Jean-Decoster, Catherine and Schmitt, Anne-Marie and Paul, Carle and Serre, Guy and Simon, Michel},

doi = {10.1096/fj.10-168658},

issn = {1530-6860 (Electronic)},

year  = {2011},

date = {2011-05-01},

journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},

volume = {25},

number = {5},

pages = {1567--1576},

abstract = {A single-nucleotide polymorphism within the gene encoding hornerin (HRNR) has recently been linked with atopic dermatitis (AD) susceptibility. HRNR shares features with filaggrin, a key protein for keratinocyte differentiation, but conflicting reports have been published concerning its expression in the epidermis, and its role is still unknown. To analyze HRNR expression and function in the epidermis, anti-HRNR antibodies were produced and used in Western blot analysis and immunohistochemical, confocal, and immunoelectron microscopy analyses of human skin and of cornified cell envelopes purified from plantar stratum corneum. We also tested whether HRNR was a substrate of transglutaminases. In the epidermis, HRNR was detected at the periphery of keratohyalin granules in the upper granular layer and at the corneocyte periphery in the whole cornified layer. Detected in Western blot analysis as numerous bands, HRNR was relatively insoluble and only extracted from epidermis with urea and/or reducing agents. The presence of HRNR in the purified envelopes was confirmed by immunoelectron microscopy and by Western blot analysis after V8-protease digestion. HRNR was shown to be a substrate of transglutaminase 3. These data demonstrate that HRNR is a component of cornified cell envelopes of human epidermis. Its reduced expression in AD may contribute to the epidermal barrier defect observed in the disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jonca2011b,

title = {Corneodesmosomes and corneodesmosin: from the stratum corneum cohesion to the pathophysiology of genodermatoses.},

author = {Jonca, Nathalie and Leclerc, Emilie A and Caubet, Cécile and Simon, Michel and Guerrin, Marina and Serre, Guy},

doi = {10.1684/ejd.2011.1264},

issn = {1167-1122 (Print)},

year  = {2011},

date = {2011-05-01},

journal = {European journal of dermatology : EJD},

volume = {21 Suppl 2},

pages = {35--42},

abstract = {Corneodesmosin (CDSN) was identified 20 years ago by raising monoclonal antibodies against human plantar stratum corneum. The protein is specific to corneodesmosomes, cell-junction structures that, in humans, are found in the epidermis, the hard palate epithelium, and the inner root sheath of the hair follicles. Synthesized by the granular keratinocytes and secreted via the lamellar bodies, CDSN is incorporated into the desmoglea of the desmosomes, shortly before their transformation into corneodesmosomes during cornification. CDSN displays adhesive properties, mostly attributable to its N-terminal glycine-rich domain, and is sequentially proteolyzed as corneocytes migrate towards the skin surface prior to desquamation. The recent inactivation of Cdsn in mice induced a lethal epidermal barrier disruption and hair follicle degeneration, related to corneodesmosome dysfunction. That confirmed the essential role of the protein in maintaining integrity of the epidermis and the hair follicle. The CDSN gene is located in PSORS1, the major psoriasis susceptibility locus on the chromosome 6, but to date its involvement in the disease pathophysiology is not clear. By contrast, two different monogenic diseases associated with nonsense mutations in CDSN, were recently identified. First, hypotrichosis simplex of the scalp in which mutated CDSN accumulates in the dermis and forms amyloid deposits; then, peeling skin disease in which the genetic defect induces dyscohesion of the stratum corneum, responsible for abnormal desquamation and increased skin penetration of allergens.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Leclerc2011,

title = {The ubiquitous dermokine delta activates Rab5 function in the early endocytic pathway.},

author = {Leclerc, Emilie A and Gazeilles, Leila and Serre, Guy and Guerrin, Marina and Jonca, Nathalie},

doi = {10.1371/journal.pone.0017816},

issn = {1932-6203 (Electronic)},

year  = {2011},

date = {2011-03-01},

journal = {PloS one},

volume = {6},

number = {3},

pages = {e17816},

abstract = {The expression of the recently identified dermokine (Dmkn) gene leads to four families of proteins with as yet unknown functions. The secreted $alpha$, $beta$ and $gamma$ isoforms share an epidermis-restricted expression pattern, whereas the $delta$ isoform is intracellular and ubiquitous. To get an insight into Dmkn$delta$ function, we performed yeast two-hybrid screening and identified the small GTPases Rab5 as partners for Dmkn$delta$. The Rab5 proteins are known to regulate membrane docking and fusion in the early endocytic pathway. GST pull-down assays confirmed the direct interaction between Rab5 and Dmkn$delta$. Transient expression of Dmkn$delta$ in HeLa cells led to the formation of punctate structures colocalized with endogenous Rab5 and clathrin, indicating Dmkn$delta$ involvement in the early steps of endocytosis. Dmkn$delta$ indeed colocalized with transferrin at early stages of endocytosis, but did not modulate its endocytosis or recycling kinetics. We also showed that Dmkn$delta$ was able to bind both inactive (GDP-bound) and active (GTP-bound) forms of Rab5 in vitro but preferentially targeted GDP-bound form in HeLa cells. Interestingly, Dmkn$delta$ expression rescued the Rab5S34N-mediated inhibition of endosome fusion. Moreover, Dmkn$delta$ caused the enlargement of vesicles positive for Rab5 by promoting GTP loading onto the small GTPase. Together our data reveal that Dmkn$delta$ activates Rab5 function and thus is involved in the early endosomal trafficking.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mattiuzzo2011,

title = {A large-scale multi-technique approach identifies forty-nine new players of keratinocyte terminal differentiation in human epidermis.},

author = {Mattiuzzo, Nicolas R and Toulza, Eve and Jonca, Nathalie and Serre, Guy and Guerrin, Marina},

doi = {10.1111/j.1600-0625.2010.01188.x},

issn = {1600-0625 (Electronic)},

year  = {2011},

date = {2011-02-01},

journal = {Experimental dermatology},

volume = {20},

number = {2},

pages = {113--118},

abstract = {At the latest stage of terminal differentiation in the epidermis, granular keratinocytes (GKs) undergo cornification, a programmed cell death required for the establishment of a functional skin barrier. A complex genetic regulatory network orchestrates the underlying biochemical modifications, but very few transcription factors specific to this programme have been identified to date. Here, we describe a large-scale, multi-technique approach performed on cells purified from normal human epidermis, primarily focusing on the identification of regulators. We combined data from microarray analysis of cell fractions enriched in GKs or basal keratinocytes, from an expressed sequence tag (EST) library built from GKs and from an in silico promoter analysis of 52 differentiation-associated genes. Among 3576 genes potentially expressed in GK, 298 candidates were selected, and half were directly profiled for the first time in the different layers of the epidermis by quantitative real-time PCR. Forty-nine genes upregulated during terminal differentiation, associated with numerous function of GK including lipid synthesis and secretion, were identified. Of 94 transcription factors detected, 37 were found to be either positively or negatively regulated, suggesting their involvement as regulators of gene expression in the GKs. These results largely extend the number of genes known as involved in the latest step of the terminal differentiation of human epidermis as well as the number of transcription factors known to control the expression of these genes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vasilopoulos2011,

title = {The 3'-UTR AACCins5874 in the stratum corneum chymotryptic enzyme gene (SCCE/KLK7), associated with atopic dermatitis; causes an increased mRNA expression without altering its stability.},

author = {Vasilopoulos, Yiannis and Sharaf, Nazar and di Giovine, Franco and Simon, Michel and Cork, Michael J and Duff, Gordon W and Tazi-Ahnini, Rachid},

doi = {10.1016/j.jdermsci.2010.11.013},

issn = {1873-569X (Electronic)},

year  = {2011},

date = {2011-02-01},

booktitle = {Journal of dermatological science},

journal = {Journal of dermatological science},

volume = {61},

number = {2},

pages = {131--133},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Paul2011,

title = {Prevalence and risk factors for xerosis in the elderly: a cross-sectional epidemiological study in primary care.},

author = {Paul, C and Maumus-Robert, S and Mazereeuw-Hautier, J and Guyen, C N and Saudez, X and Schmitt, A M},

doi = {10.1159/000334631},

issn = {1421-9832 (Electronic)},

year  = {2011},

date = {2011-01-01},

journal = {Dermatology (Basel, Switzerland)},

volume = {223},

number = {3},

pages = {260--265},

abstract = {BACKGROUND: Limited information is available concerning the prevalence and risk factors of xerosis in the elderly. OBJECTIVE: To establish the prevalence of xerosis and associated factors in elderly patients. METHODS: A national, multicenter, observational, cross-sectional study in patients aged 65 or older was performed. The data collected by general practitioners were demographics and medical history, including history of atopic disease. Xerosis was evaluated using the Overall Dry Skin score. RESULTS: 756 patients were included. The prevalence of xerosis was 55.6%. Xerosis was significantly associated with older age (OR: 1.48, 95% CI: 1.16-1.89), female sex (OR: 1.80, 95 CI%: 1.29-2.53), treatments that can potentially cause xerosis (OR: 2.21, 95 CI%: 1.54-3.17), itching during sweating (OR: 7.11, 95% CI: 3.90-12.95), a history of dry skin (OR: 2.89, 95% CI: 1.65-5.08) and a history of atopic dermatitis (OR: 3.60, 95% CI: 1.99-6.52). CONCLUSION: Xerosis is highly prevalent in the elderly. A history of atopy, especially atopic dermatitis, is associated with an increased risk of xerosis in the elderly.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Coudane2011,

title = {Deimination and expression of peptidylarginine deiminases during cutaneous wound healing in mice.},

author = {Coudane, Fanny and Méchin, Marie-Claire and Huchenq, Anne and Henry, Julie and Nachat, Rachida and Ishigami, Akihito and Adoue, Véronique and Sebbag, Mireille and Serre, Guy and Simon, Michel},

doi = {10.1684/ejd.2011.1394},

issn = {1167-1122 (Print)},

year  = {2011},

date = {2011-01-01},

journal = {European journal of dermatology : EJD},

volume = {21},

number = {3},

pages = {376--384},

abstract = {Deimination, the conversion of protein-bound arginines into citrullines, is a post-translational modification catalyzed by a peptidylarginine deiminase (Pad). In the epidermis, three Pads are expressed, namely Pad1, 2 and 3, and the major deiminated protein is filaggrin. Deimination of fibrin has been observed in various pathological inflammatory conditions. Here, we analyzed the expression of Pads and citrullination of proteins during cutaneous wound healing, i.e. in a physiological inflammatory condition. Full-thickness punches were performed on adult mouse back skin, and wound recovery was analyzed over 10 days by immunohistology and western blotting. Pad1 was immunodetected in all the neo-epidermis. Pad3, normally expressed in the stratum granulosum, was not detected in the hyperproliferative tongue of the neo-epidermis, but was shown to be co-localized with (pro)filaggrin in a large number of keratinocyte layers in its differentiating part. Deiminated proteins were detected in the stratum corneum of the neo-epidermis in the late phase of re-epithelialization, and in the clot and the clot-derived scab. In the clot where we only detected Pad4, one of the deiminated proteins was shown to be fibrin. Deimination of the clot proteins, and more generally wound healing and keratinocyte differentiation, seemed to be Pad2-independent, as shown using Padi2(-/-) mice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}