Role of type III interferons in promoting barrier formation at mucosal surfaces

Our body's surfaces that come into contact with the outside world (the lining of our nose, mouth, and gut) are protected by a layer of cells called epithelial cells. These cells form tight connections with each other to keep harmful pathogens like bacteria, viruses, and parasites from getting inside our body. These cells also produce special proteins called interferons, which help fight off infections. Recently, interferons were shown not only to fight pathogens but also to function when there's no infection. The interferons appear to be essential for creation of the tight connections in the cellular protective layer. This study will investigate how cells control the production of interferons and how these proteins help cells build their wall against the outside environment. Understanding this process could lead to new treatments for diseases that arise when this protective barrier breaks down. The project will provide education and training opportunities for high school students and teachers and for graduate students. Epithelial cells at mucosal surfaces form the primary barrier against environmental threats through tight junctions that regulate molecular diffusion and prevent pathogen access to subepithelial tissues. Type III interferons (IFNλs) primarily function at these surfaces as key protective cytokines against pathogens. Recently, the investigators discovered that basal IFNλ expression increases as epithelial cells polarize, and this increase is fundamental for regulating tight junctions and barrier function. This work identifies a previously unknown IFNλ function: controlling epithelial cells' primary role of forming tight barriers. This project will focus on understanding these mechanisms as a step towards comprehending IFNλs' complete role in mucosal surface protection beyond their established antipathogen functions. The outcomes could potentially reveal new therapeutic targets for barrier dysfunction diseases. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.