Lay Summary
Proposal No. IBD-0203
Principal Investigator: Fiona M. Powrie, DPhil
Applicant Organization: University of Oxford (United Kingdom)
Project Title: Role of TGF-β in the pathogenesis of IBD
Period of Award: August 1, 2007 – February 28, 2010
The causes of IBD remain unknown, but it is thought to result from sustained activation of the gut’s immune system, driven by the presence of normal resident bacteria. In the mouse model of colitis we have shown that a specialized group of white blood cells called regulatory T cells (TR) can not only suppress, but more importantly, cure IBD in mice. These cells represent about 5-10% of total lymphocytes in humans and given their therapeutic capability it is of utmost importance to understand the factors that control their function. Early studies showed that the immune regulatory cytokine transforming growth factor, (TGF-β) plays a key role in TR-mediated control of intestinal inflammation. Studies in humans have shown that large amounts of TGF-β are present in the colon of IBD sufferers, however, there is evidence that activated cells from the intestine of IBD patients do not respond to the suppressive properties of TGF-β suggesting that TGF-β is not functioning. In this project we will characterize how TGF-β influences the balance between protective TR and potentially harmful T effector responses in the human intestine and how this may change in IBD. Further understanding of the interactions between TGF-β and TR cells may lead to the development of targeted anti-inflammatory strategies for IBD patients.