The purpose of this application is to obtain support for a proposed conference entitled Experimental Models of Immune Dysregulation and Mucosal Inflammation. In recent years it has become apparent that a variety of genetically determined or experimentally induced abnormalities of immune function in mice leads to a common outcome, the development of chronic mucosal inflammatory bowel disease bearing a striking resemblance to one of the two major forms of human inflammatory bowel disease, Crohn's disease or ulcerative colitis. This new information is of interest to basic immunologists because it provides models with which to study the regulation of responses to exogenous non- self antigens that are constantly present in the mucosal environment and the related phenomenon of """"""""oral tolerance."""""""" In addition, this information is of interest to research gastroenterologists seeking the cause of inflammatory bowel disease and its treatment. The proposed conference will be organized into four segments. The first will focus on various murine models of peripheral and central tolerance with emphasis on the role of the suppressive cytokine TGF-Beta and negative signaling via CTLa-4 in tolerance induction. The second will be concerned with a discussion of the mechanisms underlying oral tolerance. The third will examine various representative murine models of mucosal inflammation, including those occurring in gene targeted mice, transgenic mice or normal mice subjected to various forms of stimulation; both models of inflammation resembling Crohn's disease and ulcerative colitis will be considered. The fourth and final segment will focus on the various approaches to the treatment of experimental inflammation and how this relates to that of human inflammatory bowel disease. Overall, this conference will provide a blueprint for future research in oral tolerance and inflammatory bowel disease.
