Initiation of Experimental Colitis by Commensal Flora

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DESCRIPTION (provided by applicant): As stated in PA-O 1-132, "there is a critical need for clinician-scientists with the medical training and research experience to investigate problems of environmentally relevant disease in humans. The linking of exposures to biologically derived toxins in the environment to clinical outcomes has been a consistent challenge." Inflammatory bowel disease (IBD) is a chronic and relapsing disease of unknown etiology. The environmental events that modulate inflammation or trigger a new round of symptoms are completely uncharacterized. In a healthy individual exposure to an intestinal biological pathogen results in a highly regulated immune response that first clears the organism and then returns to a controlled state. it is our premise that the chronic inflammation observed in IBD results from an inability of the mucosal immune response to return to this controlled state. Thus we present the following central hypothesis: Inflammation in experimental murine models of IBD is initiated by mucosal T cell responses to enterobacterial antigens. Our aim is to investigate the interaction of the microbiological environment of the gut with the host mucosal immune system, and their respective contributions to induction, perpetuation, and remission of IBD.