Role of type-I and type-III interferons in gastrointestinal homeostasis and pathogenesis

Interferon (IFN) was discovered based on interference with virus production, and three types of IFN are now defined. Since its discovery, IFN’s roles have expanded beyond viruses to diverse pathogen types, tissue homeostasis, and inflammatory disease. The gastrointestinal (GI) tract is arguably the tissue where the roles of IFN types are most distinct, with a particularly prominent role for type-III IFN in antiviral protection of the intestinal epithelium. Current studies continue to deepen our understanding of the type- and tissue-specific roles of IFN. This review highlights these advances within the GI tract, including discovery of protective roles for type-III IFNs against nonviral GI pathogens, and discovery of an antiviral homeostatic type-III IFN response within the intestinal epithelium.