Targeting the Intestinal Barrier to Regulate Mucosal Immunity in IBD and Infectious Enterocolitis

The research proposed here will explore this unanticipated interaction that has the intestinal barrier at its center. In retrospect, one might have anticipated that, as our first line of defense, the barrier would govern communication between intestinal contents and the immune system. Nevertheless, the underlying processes are almost entirely undefined. The studies described in this application will elucidate the mechanisms that regulate this communication, the means by which decreased channel activity either reduces or increases severity of IBD or infectious gastritis, respectively, and how excessive or insufficient dietary sodium impacts these processes. Further, the results will create a foundation that will help us to design a new class of therapies that modulate claudin-2 channel function. The data will also provide guidance as to whether interventions to reduce or increase channel activity are appropriate for an individual patient at a specific time, i.e. personalized medicine.