Colitis is a digestive disease characterized by inflammation of the colon. Development of colitis in T cell-specific TGF-beta1-deficient mice reveals an important function for TGF-beta1 in mucosal immune tolerance. Colitis in these mice is likely caused by abnormal immune responses to commensal bacterial antigens. To gain insights into the disease mechanisms, we are investigating:
- What are the functions of innate immune receptors in colitis?
- What are the functions of inflammatory cytokines in colitis?
Recent studies have shown that adjuvant-induced autoimmune diseases including autoimmune encephalomyelitis (EAE) and colleagen-induced arthritis (CIA) are dependent on Th17 helper T cells that secrete cytokine IL-17. In the presence of inflammatory cytokine IL-6, TGF-beta1 promotes the differentiation of Th17 cells. We have found that T cell-produced TGF-beta1 is essential for Th17 cell differentiation and the development of EAE in mice. To further explore this novel pro-inflammatory function of TGF-beta1 in autoimmune diseases, we are asking:
- How does TGF-beta1 regulate T cell responses in CIA?
- What is the therapeutic potential of targeting the TGF-beta1 pathway in arthritis?
