Grant: Operating Grant

Crohn's disease (CD) and Ulcerative colitis (UC) are common chronic inflammatory bowel diseases (IBD) of modern society. IBD patients experience symptoms such as abdominal pain, cramping, weight loss, fever, fatigue, nausea/vomiting and diarrhea. The incidence of IBD is rising, especially in Canada, where its prevalence is said to be among the highest in the world. Inflammation and tissue injury characteristic of CD can be found anywhere along the digestive tract while that of UC is restricted to the colon. The disease pathogenesis is thought to result from an inappropriate, exaggerated immune response in genetically-prone individuals. The currently available therapies for IBD, more particularly CD are often associated with serious side effects and highlight the need for continued research in this field. Dendritic cells (DCs) are a specialized cell type implicated in the initiation and perpetuation of immune responses. Therefore, when dysregulated, DCs may misinterpret a harmless encounter as being harmful and initiate an unnecessary immune response, leading to chronic intestinal inflammation. We identified the human counterpart of the mouse DCs (CD172a+ DCs) that promote intestinal inflammation in an experimental model of CD. We further showed that CD172a+ DCs accumulate in lymphoid and inflamed gut tissues of CD patients where they represent the major source of pro-inflammatory cytokines. In this proposal, we plan to investigate the cellular origin, the molecular signature and the detailed functional properties of CD172a+ DCs. We also plan to search for these pathogenic cells in tissues of UC patients with the aim of identifying properties (for instance biomarkers) that may help in the differential diagnosis between UC and CD. As such, detailed analysis of molecular and functional characteristics of these cells may contribute to our knowledge of disease pathogenesis and/or translate into the development of new diagnosis and therapeutic targets.