Regulation of T-cell Responses in the Inflamed Intestine

Abstract

The intestinal immune system protects the mucosal surfaces from pathogenic microorganisms. On the other hand it maintains tolerance towards dietary antigens and non-pathogenic microorganisms. The immune system continuously tailors these inflammatory and tolerogenic responses to maximize host defense without unnecessary collateral damage, a balance denoted as intestinal homeostasis. CD4+ T cells play a central role in the intestinal immune system. The balance between inflammatory CD4+ effector T cells and the function of regulatory T cells in the intestinal mucosa is crucial for homeostasis as uncontrolled T-cell responses can lead to chronic inflammatory intestinal disorders like celiac disease (CD) and inflammatory bowel disease (IBD). CD is an uncontrolled inflammatory CD4+ T-cell response to the food protein gluten leading to chronic inflammation of the small intestine. Uncontrolled inflammatory CD4+ T-cell responses to commensal non-pathogenic bacteria are associated with IBD. The focus of this thesis lies on identifying immune processes that regulate T-cell responses in the intestine and to provide further insight into defective regulation of T-cell responses leading to intestinal inflammation. Better knowledge on T-cell responses is essential for understanding the etiology and pathophysiology of intestinal inflammatory diseases and for the development of novel therapies.