Crohn's disease and ulcerative colitis are the two major disease entities of inflammatory bowel disease (IBD). These two conditions are histopathologically and anatomically distinct, as Crohn's disease is characterized by transmural inflammation that can occur throughout the gastrointestinal (GI) tract and ulcerative colitis is characterized by more superficial inflammation confined to the colon and rectum. Despite these differences, compelling evidence generated from studies of human patients and experimental models indicate that both disorders are dependent upon factors present within the complex intestinal microbiota. However, how microbiota regulates chronic intestinal inflammation is still not completely understood. My research focuses on host immune response to microbiota and the pathogenesis of inflammatory bowel diseases (IBD), specifically on how T cell, B cell and dendritic cell response to microbiota, how microbiota regulates mucosal immune system, and the role of this interplay in the pathogenesis of IBD, and also the development of mucosal adjuvants. Our hypothesis is that IBD is mediated by a restricted set of pathogenic CD4+T cells responding to microbiota, the antigens to which the host is normally tolerant. Innate cells and TLR ligands play a critical role in activation and expansion of pathogenic T cells. microRNAs regulate host response to enteric bacterial antigens and pathogenesis of IBD. A number of research projects are underway in my laboratory and these NIH-funded studies involve a number of significant collaborations both at UTMB as well as with other Universities and Research Institutes. Specifically, individual projects include: 1) The role of Th1, Th17, and Treg cells reactive to commensal bacterial antigens in mucosal Immunity and pathogenesis of IBD. 2) Plasticity and stability of memory Th1, Th17, and Treg cells in intestine and their role in progression of IBD. 3) microRNA regulation of host response to commensal bacteria and pathogenesis of IBD. 4) The mechanisms of mucosal adjuvants in promoting immune responses.