Immunomodulation of regulatory mechanisms in mucosal immunity

Inflammatory bowel diseases (IBD) are chronic conditions characterized by severe inflammation of parts of the bowel, causing significant symptoms, such as diarrhea, pain and intestinal bleeding. There are two main types of IBD: Crohn’s disease and ulcerative colitis. IBD is prevalent in Canada, with an estimated 170,000 people suffering from the disease. Despite years of effort, the causes of these disorders remain incompletely and inadequately understood. The intestinal inflammation in IBD is thought to result from abnormal responses to the bacteria that live normally in the gut. In healthy individuals, the immune system is able to distinguish between harmless (commensal) bacteria and those that cause infections (pathogens). In IBD patients, the immune system elicits an aberrant and aggressive response against components of host commensal bacteria. Dendritic cells (DC) and regulatory T cells (nTreg) are two types of cells important in maintaining a healthy intestinal immune system. Defects in the development or function of these cells could ultimately lead to inappropriate responses to commensal bacteria, or certain commensal bacteria or pathogens could perturb the normal immune state of the gut. Dr. Gijs Hardenberg is investigating the interplay between host commensal bacteria and the immune system in IBD. He is studying the roles of nTreg and immune responses, focusing on the bacterial protein flagellin, which has been shown to be the major target of intestinal immune responses in Crohn’s disease patients. His work aims to understand how IBD begins and persists how it might ultimately be treated or even prevented. The findings from these studies may also be broadly applicable to other autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and lupus.