Comparative Functional Analysis of 12 Mammalian IFN-?4 Orthologs

Paquin, Ashley; Onabajo, Olusegun O.; Tang, Wei; Prokunina-Olsson, Ludmila

IFNs are classified into three major groups-types I, II, and III-based on their receptor utilization. Type-I IFNs include a panel of IFN-a subtypes, IFN-b, IFN-e, IFN-k, and IFN-o, all of which signal through a ubiquitous IFNAR receptor complex, consisting of the IFNAR1 and IFNAR2 receptors. IFN-g, the only known type-II IFN, signals through its own receptor complex, IFNGR, consisting of the IFNGR1 and IFNGR2 receptors. Type-III IFNs (IFN-l1-4) signal through the IFNLR receptor complex, which consists of the IFNLR1 receptor specific to type-III IFNs, and the IL10R2 receptor shared by all type-III IFNs and the IL-10 family of cytokines. The signaling of type-III IFNs is restricted compared with other IFNs because expression of IFNLR1 is largely limited to epithelial cells, such as of the respiratory and gastrointestinal tract. IFN activity in these cells, which are commonly exposed to exogenous pathogens, is important for prevention of viral entry and dissemination.