Grant: Project Grant

Inflammatory bowel disease (IBD) likely result from deregulated immune responses to the indigenous microorganisms that reside within the intestine, collectively termed the microbiota, in genetically susceptible hosts. The intestine contains a large number of different immune cells that have the delicate task of fighting off pathogens while "keeping the peace" with the resident microbes. Of these immune cells, T cells are central to maintaining the status quo, and deregulated T cell responses are believed to be at the core of IBD. This past decade has revealed the importance of the microbiota in health and disease, and how it influences the immune system, including the function of different types of T cells. Invariant Natural Killer T (iNKT) cells are a type of T cells that can regulate immune responses during numerous diseases such as cancer, autoimmunity and inflammation. Specifically, iNKT cells play protective or deleterious functions in animal models of Crohn's disease (CD) and ulcerative colitis (UC), respectively. Moreover iNKT cell defects have been found in CD patients. These cells are particularly well equipped to recognize microbes and therefore protect from pathogens. However, their interaction with the commensal microbiota remains elusive. Our previous research has shown that mice deficient in iNKT cells have an altered and pro-inflammatory microbiota. This research project will build on these findings to explore how iNKT cells and the microbiota influence each other, and the impact of this bidirectional relationship on the establishment of intestinal inflammation. Identification of these mechanisms may lead to new therapeutic strategies targeting iNKT cells for the treatment of IBD.