Type I interferon receptor (IFNAR) (IFNAR)

The Type I interferon receptor, known as IFNAR, is a heterodimeric cell-surface receptor complex composed of IFNAR1 and IFNAR2 subunits that binds type I interferons such as IFNα, IFNβ, IFNω, and others to initiate innate immune responses. Expressed on nearly all nucleated cells, it features IFNAR2 as the high-affinity ligand-binding chain and IFNAR1 as essential for signal transduction via its unique four-domain extracellular structure. Ligand binding induces a ternary complex that activates membrane-proximal Janus kinases (JAK1 on IFNAR2 and Tyk2 on IFNAR1), phosphorylating STAT1 and STAT2 to form the ISGF3 transcription factor, which drives expression of hundreds of interferon-stimulated genes (ISGs) promoting antiviral defense, cell proliferation inhibition, and immune cell activation including NK cells and macrophages. In disease, IFNAR signaling suppresses tumor growth by inhibiting angiogenesis and enhancing immune recognition but is dysregulated in cancers where tumors evade it, as well as in autoimmune interferonopathies from pathway hyperactivity. Therapeutically, recombinant IFNα and IFNβ target IFNAR for treating viral infections, melanoma, leukemia, and multiple sclerosis, though challenges include dose-limiting toxicities like flu-like symptoms and signal desensitization via USP18-mediated IFNAR1 interference.

Other names

IFN-α receptorIFN-α/β receptorIFNAR1/IFNAR2 receptor complexReceptor interferon alpha-beta

Binding of type I IFNs (e.g., IFNα, IFNβ) to IFNAR1 and IFNAR2 forms a ternary complex that activates JAK1 and Tyk2 kinases, leading to phosphorylation of STAT1/STAT2, formation of ISGF3 transcription factor, and induction of interferon-stimulated genes (ISGs) for antiviral, antiproliferative, and immunomodulatory effects