Research Summary

Interplay between effector and regulatory T cells in the pathogenesis of intestinal inflammation.

Inflammatory Bowel Disease (IBD), comprised of Crohn's Disease (CD) and ulcerative colitis (UC) are severe disorders of the gastrointestinal tract. IL-12- induced Th1 cells were thought to be major effector cells to develop colitis as neutralization of IL-12 prevents tissue inflammation in colitis. Interestingly, IFN-g deficient T cells were still induce disease suggested the role of other helper T cell subset other than Th1 cells in disease induction.

Recently discovered Th17-IL-23R axis plays a critical role in the development of IBD, as IL-23-/- and IL-23R-/- mice are resistant to development of colitis. The mechanism by which IL-23 induces pathogenic functions of Th17 cells and restrains the functions of regulatory T cells (Foxp3+ Tregs and IL-10+ Tr1 cells) is not clear. We will be identifying the mechanisms of interplay of effector (Th17 cells) and regulatory T cells (Foxp3+ Tregs and IL-10+ Tr1 cells) in context of IL-23 functions in the intestinal inflammation in IBD. 

Understanding the mechanism of induction pathogenic TH17 cells. The antigenic stimulation of naïve T cells in the presence of TGF and IL-6 initiate the TH17 differentiation pathway. Exposure of IL-23 to TH17 cells not stabilizes phenotype of these cells but also induces the pathogenic feature of these cells. However, the mechanism by which IL-23 induces the pathogenic Th17 cells is not clearly understood.