StemIBD

Inflammatory bowel disease (IBD) is characterized by severe gut inflammation associated with various extra-intestinal inflammatory manifestations, affecting up to 50% of patients and causing even greater morbidity than the intestinal disease itself. Inflammatory CD4+ T cells, particularly Th17 cells, play an important role in this pathology, and at the same time these cells are essential for the integrity of the epithelial barrier and host defense against infection. However, the origin of this dichotomy within Th17 cells remains unclear. In several mouse models of colitis, our preliminary results showed that these Th17 cells are indeed heterogeneous. They contain several subsets including effector cells and a pool of stem-like cells. Interestingly, our preliminary results suggest that this pool of stem-like cells may constitute a reservoir from which pathogenic T cells can differentiate and contribute to IBD. Our overall aim is to decipher the cellular and molecular mechanisms that control the generation of the stem-like pool and the factors that influence their program of differentiation into inflammatory T cells. The originality of this project is the combination of murine models and patient biopsies in order to address the unresolved mechanisms that control the origin and maintenance of Th17 stem-like cells, as well as their differentiation and contribution to IBD. Our results will help to improve and/or propose new therapeutic strategies for IBD and associated extra-intestinal inflammatory manifestations.