Inflammatory Bowel Diseases, including Crohn’s disease and ulcerative colitis are characterized by chronic intestinal inflammation and tissue damage. There are trillions of bacteria found within the human intestine and IBDs are thought to develop when mucus barriers that normally keep these bacteria inside the gastrointestinal tract become impaired, allowing bacteria to escape out of the gut lumen and causing chronic inflammation. While the role of epithelial cells in promoting barrier function is well known, the protective actions of the mucus barrier are relatively understudied.
Specialized secretory epithelial cells known as goblet cells within the gut lumen produce mucins known as Muc2 and pro-inflammatory proteins called RELM-ß. Through in vitro and in vivo studies, and microbiota analysis, Morampudi plans to define how these goblet cell proteins cooperatively protect the intestine from developing spontaneous colitis through the development of these products.Through tests with micelacking either Muc2 or RELM-ß, Dr. Morampudi has hypothesized that both proteins act together to protect the intestine from gut commensal bacteria. Muc2 provides a structural barrier, preventing bacteria from contacting the immune system, but when the mucus barrier is impaired, RELM-ß is induced to create an antimicrobial zone above the intestinal epithelium. Under conditions where expression of both proteins is impaired (such as by ER stress), the commensal bacteria are able to escape from the intestine and cause colitis/IBD.Ultimately, this research will provide insights as to how the development of spontaneous colitis can be prevented.