Grant: Fellowship - Priority Announcement: Gastroenterology

Patients with Inflammatory Bowel Disease (IBD) suffer bouts of extreme gut inflammation that disrupt the population of bacteria in their intestines. Thus IBD patients often have fewer beneficial bacteria and suffer an overgrowth of potentially dangerous bacteria. In healthy individuals, such responses are typically prevented by SIGIRR, a protein made by the cells that line the gut. SIGIRR acts by suppressing mechanisms that drive inflammation. We have shown that loss of SIGIRR dramatically increases inflammation and drives bacterial imbalance. The inflammation can become so severe that gut tissue can become necrotic. We do not have a way to promote the beneficial actions of SIGIRR in the gut, but recently, a newly recognized anti-inflammatory compound called interleukin (IL)-37, has been shown to interact with SIGIRR to inhibit inflammatory responses in human cells. In this project, we plan to test whether IL-37 stimulates SIGIRR to: i) control inflammation and suppress bacterial killing responses in the cells that line the gut; ii) protect mice from experimentally-induced IBD; and iii) promote normal gut microbe balance. Ultimately, my studies will explore the potential for IL-37 to act as a new therapeutic for patients with IBD.