Interferon alpha and beta receptor subunit 1 (IFNAR1) (IFNAR1)

Interferon alpha and beta receptor subunit 1 (IFNAR1) is a critical component of the heterodimeric Type I interferon receptor complex, which also includes the IFNAR2 subunit [1, 3]. As a member of the type II cytokine receptor family, IFNAR1 is a single-pass transmembrane protein that serves as a universal receptor for all type I interferons, including IFN-alpha, IFN-beta, IFN-omega, and IFN-kappa [1, 12]. Upon ligand binding, IFNAR1 associates with IFNAR2 to form a ternary complex, triggering the activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, primarily through the kinases TYK2 and JAK1 [8, 11]. This signaling cascade leads to the nuclear translocation of STAT complexes and the transcription of hundreds of interferon-stimulated genes (ISGs) that mediate potent antiviral, antiproliferative, and immunomodulatory effects [8, 10]. In clinical contexts, dysregulated IFNAR1 signaling is a hallmark of various pathologies. Overexpression or chronic activation of the type I interferon pathway is strongly associated with autoimmune disorders, most notably systemic lupus erythematosus (SLE), where it drives persistent inflammation and tissue damage [8, 14]. Conversely, genetic deficiencies in IFNAR1 lead to severe immunodeficiency and increased susceptibility to life-threatening viral infections, such as COVID-19 and herpes simplex encephalitis [1, 15]. Therapeutically, IFNAR1 is a major target for drug development; for instance, the monoclonal antibody anifrolumab is an FDA-approved antagonist that blocks the receptor to treat SLE [12, 13]. Additionally, recombinant type I interferons act as agonists at this receptor for the treatment of chronic viral hepatitis and multiple sclerosis [5, 17].

Other names

Interferon alpha/beta receptor 1Type I interferon receptor 1IFNARIFRCCytokine receptor class-II member 1Cytokine receptor family 2 member 1IFN-alpha/beta receptor 1Interferon (alpha, beta and omega) receptor 1CRF2-1IFN-R-1Interferon-alpha/beta receptor alpha chainAlpha-type antiviral proteinBeta-type antiviral proteinInterferon-beta receptor 1IFN-alpha-RECIFNBRAVP

Antagonism of the extracellular domain to block ligand binding and ternary complex formation; Agonism via recombinant ligand binding to initiate signaling [8, 11, 12].