Interferon alpha and beta receptor subunit 1 (IFNAR1)

The Interferon alpha and beta receptor subunit 1 (IFNAR1) is a critical component of the heterodimeric receptor complex that mediates the biological effects of type I interferons, including IFN-alpha, IFN-beta, and IFN-omega [1.2.1, 1.2.5]. Upon ligand binding, IFNAR1 associates with IFNAR2 to activate the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, which triggers the expression of hundreds of interferon-stimulated genes (ISGs) [1.3.1, 1.4.1]. These genes play essential roles in antiviral defense, cell growth regulation, and immune modulation [1.3.2, 1.4.2]. Dysregulation of IFNAR1 signaling is implicated in various pathologies; overactivity is a hallmark of autoimmune diseases like systemic lupus erythematosus (SLE), while deficiency or downregulation can lead to severe viral susceptibility or immune evasion by tumors [1.1.1, 1.1.4, 1.4.1]. Therapeutically, IFNAR1 is a major target for treating SLE, with the monoclonal antibody anifrolumab acting as a direct antagonist to block the binding of all type I interferons [1.4.3, 1.4.4]. Conversely, agonists or the interferons themselves have been used to treat viral infections and certain cancers by stimulating the receptor's antiviral and antiproliferative activities [1.4.2]. Monitoring the "interferon signature"—a panel of IFN-inducible genes—serves as a key biomarker for assessing disease activity and treatment response [1.1.2, 1.1.3]. Safety concerns associated with IFNAR1 blockade primarily involve an increased risk of viral infections, such as herpes zoster, due to the suppression of the body's natural antiviral defenses [1.4.3].

Other names

IFNARIFRCInterferon alpha/beta receptor 1Type I interferon receptor 1Cytokine receptor class-II member 1Cytokine receptor family 2 member 1IFN-R-1CRF2-1IFN-alpha/betaRalphaIFN-alpha/betaR1IFNBRAVPIMD106

Anifrolumab is a human monoclonal antibody that binds to the subunit 1 of the type I interferon receptor (IFNAR1), sterically inhibiting the binding of type I interferons (such as IFN-alpha, IFN-beta, and IFN-omega) and preventing the formation of the active ternary signaling complex, thereby blocking the downstream JAK-STAT signaling pathway and the expression of interferon-stimulated genes (ISGs) [1.4.3, 1.4.4]. Agonists like interferon-alpha and interferon-beta bind to the receptor to initiate the JAK-STAT cascade, promoting antiviral and immunomodulatory responses [1.4.2].