Grant: Project Grant

Ulcerative colitis (UC) is a life-long disease that causes serious gut damage. Over 150,000 Canadians live with UC and this number is rapidly rising especially in children. Available drugs work for some people but can cause side effects. These drugs also stop working over time. Immune proteins called type III interferons (IFN-lambdas, IFN-Ls) were originally discovered for how they help our body fight viruses. IFN-Ls are also made in a healthy gut where they promote a strong gut barrier and inhibit inflammation, unlike other IFN proteins. IFN-Ls are also essential for gut healing when the gut is damaged, like what happens in UC. Thus, IFN-Ls may protect against UC and help maintain a healthy gut. We recently found for the first time that IFN-L functions are decreased in the gut of some UC patients. This means these UC patients could have worse symptoms and greater barrier damage due to the loss of beneficial IFN-L actions. We still do not fully understand how IFN-Ls help human gut immunity since most studies have used animal models where IFN-L acts differently. In this study, we will study fresh gut tissues and blood collected from people with or without UC during their routine clinic visits. We will use a combination of our novel human biopsy culture model, 3D 'mini-guts' and immune cells to find out exactly how IFN-L promotes gut health, but also how IFN-L could dampen the overreactive immune cells causing symptoms. We will also find out which specific gut factors control how IFN-Ls work to help uncover how to restore optimal IFN-L anti-inflammatory actions. Our long-term goal is to fully understand how IFN-L works in a healthy gut versus how it is changed in UC and to develop new treatments that promote IFN-L activity to help improve UC patient outcomes.