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Person in charge of the Unit : Oui
Humoral immune protection against pathogens relies on the development of high affinity antibodies produced by activated B cells that differentiated further in memory B cells or long-lived plasma cells. This process takes place in the germinal centers and depends on a subset of CD4+ T cells called T follicular helper (Tfh). Although many studies are devoted to this novel T helper cell population, the molecular mechanisms governing Tfh cell differentiation have yet to be characterized and better understanding of this crucial immune process would have major implications in immune disease treatment and vaccine formulation. In particular modulating Tfh cell activation in vivo may help to develop long term humoral responses that lack allergic, IgE-mediated side effects. Our research group has demonstrated IL-6 promotes the differentiation of naïve T cells into follicular helper T cells. IL-6 appears to control Tfh differentiation in a STAT3 dependent fashion, suggesting an important role for this transcription factor in the control of humoral responses. STAT3 activation also allowed the conversion of Th2 cells into Tfh cells, suggesting that some 'plasticity' exist between T helper cells and highlighting a possible role for the IL-6 / STAT3 signaling pathway in the conversion of pathogenic allergic (IgE) Th2 responses into protective (IgG) humoral Tfh responses.Our current research objective is to identify the molecular mechanism by which STAT3 controls T cells differentiation. In particular, our project aims at understanding the functional relationship between STAT3 and other transcription factors (such as BCL6 and cMAF) known to play a role in T follicular helper differentiation and function. Finally, based on recent finding indicating a role for cell metabolism in the control of T cell differentiation, we plan to explore the possible relationship between intracellular levels of important metabolites (such as NAD and ATP) and STAT3 activation. This novel avenue of research may shed light on a possible link between the nutritional status and the development of humoral immune responses, a finding of potential clinical relevance in the field of vaccination.