Researchers will collaborate to see whether autoimmune inflammatory bowel disease (called Crohn's disease) is related to alterations of a specific gene, which results in impaired regulation of immune T cells that cannot differentiate harmful from harmless bacteria.
Crohn's disease is characterized by a chronic inflammation of the small and large intestine. This inflammatory response is produced by patients' immune T cells which mistake all bacteria as harmful and forge a relentless attack. Prior population-based studies have linked Crohn's disease with three types of alterations in the "NOD2" gene. This gene produces a receptor on T cells that enables the T cells to recognize a constituent of the outer wall of bacteria. In the case of harmless bacteria, certain regulatory T cells keep other T cells from attacking these bacteria.
In Crohn's disease patients, however, the investigators hypothesize that the NOD2 gene alterations render regulatory T cells unable to receive a signal they need to survive. Without the signal, the regulatory T cells literally grow themselves to death. Without sufficient surviving regulatory T cells, Crohn's disease patients' errant T cells are unrestrained and constantly attack the harmless bacteria, producing chronic inflammation. The collaborators will test this hypothesis in the cells of Crohn's disease patients.
Significance: If the study unearths the way in which genetic alterations result in chronic inflammatory bowel disease, the results could lead to a new diagnostic test of regulatory T cell dysfunction, a new method for measuring disease activity, and new approaches to treating deficiencies in regulatory T cells.