Molecular, Cellular, Tissue, and Organismal Functions of Type III Interferons

Type III interferons are essential immune mediators playing pleiotropic roles during health and disease. In this review, we highlight the molecular and cellular pathways that lead to the production of type III interferons. We also describe their exquisite capacity to act at primary barrier tissues such as those in the intestine, airways, urogenital tract, and skin, as well as to act in other organs such as the liver and thymus. We characterize the activity of type III interferons on distinct cell types in different tissues and organs and detail their impact for the host in the context of viral, bacterial, helminth, and fungal infections. Additionally, we illustrate roles of type III interferons during the development of inflammatory diseases such as inflammatory bowel disease, acute respiratory distress syndrome, asthma, solid tumors, and lupus. Overall, we summarize the dichotomous roles played by this class of interferons and highlight the knowledge gaps that must be addressed to harness type III interferons against multiple human diseases.