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.