Trillions of microorganisms line our intestine and play essential roles in human health. Our immune system needs to ignore these microorganisms, but be capable of attacking harmful bugs that enter the body. When this delicate balance goes wrong, inflammatory bowel disease (IBD) can occur. Understanding the molecules and pathways that control the gut immune system in health, and how these malfunction in IBD is crucial for identifying new targets for potential treatment.
Our previous work in mice identified a crucial anti-inflammatory pathway in the gut, showing that a molecule controlling the activation of a key regulator of the immune system (called TGF-beta) is critical in preventing intestinal inflammation. Our new work now shows that this anti-inflammatory pathway is present in humans, specifically on immune cells called monocytes and macrophages, but is completely absent in IBD patients.
Our proposal aims to determine why this protective pathway is missing in patients with IBD, by identifying molecular and genetic factors that are important in controlling its function. By understanding how this important anti-inflammatory pathway is regulated, we hope to identify potential ways of preventing or reversing it being switched off in patients with IBD.