@article{maire_fine-tuning_2024,

title = {Fine-tuning levels of filamins a and b as a specific mechanism sustaining Th2 lymphocyte functions},

author = {Kilian Maire and Léa Chamy and Samira Ghazali and Manon Carratala-Lasserre and Margot Zahm and Clément Bouisset and Arnaud Métais and Lucie Combes-Soia and Lidia Fuente-Vizuete and Hussein Trad and Adeline Chaubet and Magali Savignac and Anne Gonzalez de Peredo and Arun Subramaniam and Olivier Joffre and Pierre G. Lutz and Isabelle Lamsoul},

doi = {10.1038/s41467-024-53768-3},

issn = {2041-1723},

year  = {2024},

date = {2024-12-01},

urldate = {2024-12-01},

journal = {Nature Communications},

volume = {15},

number = {1},

pages = {10574},

abstract = {Augmenting the portfolio of therapeutics for type 2-driven diseases is crucial to address unmet clinical needs and to design personalized treatment schemes. An attractive therapy for such diseases would consist in targeting the recruitment of T helper 2 (Th2) lymphocytes to inflammatory sites. Herein, we show the degradation of filamins (FLN) a and b by the ASB2α E3 ubiquitin ligase as a mechanism sustaining Th2 lymphocyte functions. Low levels of FLNa and FLNb confer an elongated shape to Th2 lymphocytes associated with efficient αVβ3 integrin-dependent cell migration. Genes encoding the αVβ3 integrin and ASB2α belong to the core of Th2-specific genes. Using genetically modified mice, we find that increasing the levels of FLNa and FLNb in Th2 lymphocytes reduces airway inflammation through diminished Th2 lymphocyte recruitment in inflamed lungs. Collectively, our results highlight ASB2α and its substrates FLNa and FLNb to alter Th2 lymphocyte-mediated responses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Impact of the Multiple Sclerosis-Associated Genetic Variant CD226 Gly307Ser on Human CD8 T-Cell Functions},

author = {Elena Morandi and Véronique Adoue and Isabelle Bernard and Ekaterina Friebel and Nicolas Nunez and Yann Aubert and Frederick Masson and Anne S Dejean and Burkhard Becher and Anne Astier and Ludovic Martinet and Abdelhadi Saoudi},

doi = {10.1212/NXI.0000000000200306},

year  = {2024},

date = {2024-09-04},

urldate = {2024-09-04},

journal = {Neurol Neuroimmunol Neuroinflammation},

volume = {11},

number = {6},

abstract = {Background and Objectives

The rs763361 nonsynonymous variant in the CD226 gene, which results in a glycine-to-serine substitution at position 307 of the CD226 protein, has been implicated as a risk factor of various immune-mediated diseases, including multiple sclerosis (MS). Compelling evidence suggests that this allele may play a significant role in predisposing individuals to MS by decreasing the immune-regulatory capacity of Treg cells and increasing the proinflammatory potential of effector CD4 T cells. However, the impact of this CD226 gene variant on CD8 T-cell functions, a population that also plays a key role in MS, remains to be determined.



Methods

To study whether the CD226 risk variant affects human CD8 T-cell functions, we used CD8 T cells isolated from peripheral blood mononuclear cell of 16 age-matched healthy donors homozygous for either the protective or the risk allele of CD226. We characterized these CD8 T cells on T-cell receptor (TCR) stimulation using high-parametric flow cytometry and bulk RNAseq and through characterization of canonical signaling pathways and cytokine production.



Results

On TCR engagement, the phenotype of ex vivo CD8 T cells bearing the protective (CD226-307Gly) or the risk (CD226-307Ser) allele of CD226 was largely overlapping. However, the transcriptomic signature of CD8 T cells from the donors carrying the risk allele presented an enrichment in TCR, JAK/STAT, and IFNγ signaling. We next found that the CD226-307Ser risk allele leads to a selective increase in the phosphorylation of the mitogen-activated protein kinases extracellular signal–regulated kinases 1 and 2 (ERK1/2) associated with enhanced phosphorylation of STAT4 and increased production of IFNγ.



Discussion

Our data suggest that the CD226-307Ser risk variant imposes immune dysregulation by increasing the pathways related to IFNγ signaling in CD8 T cells, thereby contributing to the risk of developing chronic inflammation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Osma-Garcia2023b,

title = {The RNA binding proteins TIA1 and TIAL1 promote Mcl1 mRNA translation to protect germinal center responses from apoptosis},

author = {Osma-Garcia, Ines C. 

and Mouysset, Mailys 

and Capitan-Sobrino, Dunja 

and Aubert, Yann 

and Turner, Martin 

and Diaz-Mu{ñ}oz, Manuel D.},

url = {https://doi.org/10.1038/s41423-023-01063-4},

doi = {10.1038/s41423-023-01063-4},

issn = {2042-0226},

year  = {2023},

date = {2023-07-20},

urldate = {2023-07-20},

journal = {Cellular & Molecular Immunology},

abstract = {Germinal centers (GCs) are essential for the establishment of long-lasting antibody responses. GC B cells rely on post-transcriptional RNA mechanisms to translate activation-associated transcriptional programs into functional changes in the cell proteome. However, the critical proteins driving these key mechanisms are still unknown. Here, we show that the RNA binding proteins TIA1 and TIAL1 are required for the generation of long-lasting GC responses. TIA1- and TIAL1-deficient GC B cells fail to undergo antigen-mediated positive selection, expansion and differentiation into B-cell clones producing high-affinity antibodies. Mechanistically, TIA1 and TIAL1 control the transcriptional identity of dark- and light-zone GC B cells and enable timely expression of the prosurvival molecule MCL1. Thus, we demonstrate here that TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific GC B cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{CéliaDupain2018,

title = {Discovery of new fusion transcripts in a cohort of pediatric solid cancers at relapse and relevance for personalized medicine},

author = {Célia Dupain and Anne C. Harttrampf and Yannick Boursin and Manuel Lebeurrier and Windy Rondof and Guillaume Robert-Siegwald and Pierre Khoueiry and Birgit Geoerger and Liliane Massaad-Massade},

editor = {Cell Press},

url = {https://www.sciencedirect.com/science/article/pii/S152500161830529X},

doi = {https://doi.org/10.1016/j.ymthe.2018.10.022},

year  = {2018},

date = {2018-11-02},

urldate = {2018-11-02},

journal = {Molecular Therapy},

abstract = {We hypothetized that pediatric cancers would more likely harbor fusion transcripts. To dissect the complexity of the fusions landscape in recurrent solid pediatric cancers, we conducted a study on 48 patients with different relapsing/resistant malignancies. By analysing RNA-sequencing data with a new in-house pipeline for fusions detection named ChimComp, followed by verification by real time PCR, we identified and classified the most confident fusion transcripts (FT) according to their potential biological function and druggability. The majority of FT were predicted to affect key cancer pathways and described to be involved in oncogenesis. Contrary to previous descriptions, we found no significant correlation between the number of fusions and mutations, emphasizing the particularity to study pre-treated pediatric patients. A considerable proportion of FT containing tumor suppressor genes was detected, reflecting their importance in pediatric cancers. FT containing non-receptor tyrosine kinases occurred at low incidence and predominantly in brain tumors. Remarkably, more than 30% of patients presented a potentially druggable high-confidence fusion. In conclusion, we detected new oncogenic FT in relapsing pediatric cancer patients by establishing a robust pipeline that can be applied to other malignancies, to detect and prioritize experimental validation studies leading to the development of new therapeutic options.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}