Grant: Operating Grant

Chronic inflammatory bowel diseases (IBD) include Crohn's disease and ulcerative colitis. IBD is most often diagnosed in young subjects aged 20 to 30 years but can occur at any age: 15% of cases involving children. The origin of IBD is poorly understood, and researchers believe that several factors are involved in their appearance. They may be due to an abnormal response of the intestinal immune system to the bacterial flora in genetically predisposed individuals. Genetic studies have identified many susceptibility genes, which allowed a better understanding of the immune and inflammatory pathways involved in these diseases. Recently, the presence of two polymorphisms in the gene coding for SHP-2 protein has been associated with a greater susceptibility to develop ulcerative colitis. Aside from these observations, previous work from Pre Rivard showed that knockout mice for the expression of SHP-2 in the intestinal epithelium rapidly develop severe inflammation in this tissue. This inflammation is caused by the hypersensitivity of the epithelium to some components of the bacterial flora present in the intestinal lumen. Taken together, our data suggest that SHP-2 is functionally important to maintain the barrier function of the intestine for its defence against the intestinal microbes. This project proposes to unravel the mechanisms by which SHP-2 controls this process.