Tracking and modulation of regulatory T cells in a disease model of autoimmunity.

Crohns disease (CD) and ulcerative colitis are chronic disabling inflammatory bowel diseases (IBD) with increasing prevalence throughout the world. The chronic inflammation leads to complications as a result of insufficient mucosal healing (ulcers, fistula) and excessive healing in the deeper layers (strictures, fibrosis). Fibrosis has a major clinical impact on the disease course, but we dont have a good knowledge of the time to fibrosis development, nor of the pathophysiology involved. Moreover anti-fibrotic therapies have not been identified in IBD. The lack of reliable animal models to study fibrosis and the lack of serologic or imaging bio-markers of fibrosis has hindered the development of new therapies. Recently, it has become clear that the innate immune response and non-classical immune cells (such as mesenchymal cells) play an important role in the induction of fibrosis. Innate lymphoid cells (ILC) have recently been identified as effectors of innate immunity and regulators of tissue remodeling. In this project, we aim to unravel the role of ILC in the pathophysiology of chronic colitis and in the induction of fibrosis. ILC will be characterized in a murine model of chronic colitis and the kinetics of tissue infiltration in relation to the induction of fibrosis will be studied. Interventional studies will further delineate the role of these cells in fibrosis. The findings will be translated from bench to bedside by studying ILC in blood and intestinal biopsies of IBD patients. This translational project aims to provide new insights into the pathogenesis of chronic colitis and into induction of fibrosis and eventually to new therapeutic targets in IBD, especially in the prevention of fibrotic complications.

Keywords:Modulation of regulatory T cells

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences