IL-37 signaling via SIGIRR: A novel mechanism to suppress intestinal epithelial cell driven inflammation and dysbiosis

Patients with Inflammatory Bowel Disease (IBD) suffer bouts of extreme gut inflammation that disrupt the population of bacteria in their intestines. Consequently, 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. Loss of SIGIRR dramatically increases inflammation and drives bacterial imbalance. The inflammation can become so severe that gut tissue can become necrotic. Currently, there is no way to promote the beneficial actions of SIGIRR in the gut. Recently, however, a newly recognized anti-inflammatory compound called interleukin (IL)-37 has been shown to interact with SIGIRR to inhibit inflammatory responses in human cells. 

Dr. Allaire will test whether IL-37 stimulates SIGIRR to: control inflammation and suppress bacterial killing responses in the cells that line the gut; protect mice from experimentally-induced IBD; and promote normal gut microbe balance. Results from this study will include an evaluation of the potential for IL-37 to act as a new therapeutic for patients with IBD.