Nathalie Schmitt - Pathways promoting the differentiation of T follicular helper cells in humans

T follicular helper (Tfh) cells are a subset of CD4 T cell specialized in providing help to B cells. Tfh cell response needs to be regulated because a too strong Tfh response can lead to autoimmunity while a too weak Tfh response leads to insufficient antibody response to pathogens. Therefore, elucidating the pathways associated with Tfh cell differentiation is of prime importance to understand how Tfh cell responses are regulated in vivo. Our research has identified several key factors promoting Tfh cell differentiation in humans. We first reported that the Th1-promoting cytokine IL-12 induces human naïve CD4 T cells to become IL-21 producing cells that share phenotypical and functional properties with Tfh cells in vitro. We further demonstrated that children deficient for IL-12 receptor subunit present a diminished Tfh and B cell responses, indicating that IL-12 signals are indeed important for optimal Tfh cell responses in vivo in humans. Given the importance of IL-12 for both Tfh and Th1 cell differentiation in humans, we suspected the presence of other factor(s) that acts together with IL-12 to promote the differentiation of Tfh cells. By using a systematic approach, we found that TGF-beta provides critical additional signals to promote initial Tfh differentiation in humans. Last, we recently reported that the co-stimulatory molecule OX40L expressed by antigen-presenting cells also promotes the differentiation of human naïve and memory CD4 T cells into functional B helper Tfh cells. Our study indicates that multiple pathways are involved in promoting Tfh cell differentiation in humans, and suggests that dysregulation of these pathways is involved in the pathogenesis of human autoimmune diseases.

2^nd IGO meeting

La seconde édition des conférences organisées par le Labex IGO (IGO meeting) s’est déroulée les 21 et 22 avril 2016 à la Faculté de pharmacie de Nantes. Cette conférence a rassemblé 160 spécialistes de l’immunologie, de la transplantation et de l’oncologie. Des orateurs français et étrangers (USA, Grande-Bretagne, Pays-Bas, Espagne, Italie, Suisse) sont venus exposer leurs travaux et les dernières avancées dans leurs domaines de recherche. Des sessions (communications orales et posters) étaient également réservées aux jeunes chercheurs pour qu’ils puissent présenter leurs travaux et ainsi favoriser les échanges avec leurs collègues et les chercheurs séniors. Ce 2^nd IGO meeting, en créant un environnement propice à l’initiation de nouvelles collaborations à l’intérieur et au-delà du périmètre du Labex IGO, a été un vrai succès scientifique.