Interferon-gamma receptor (IFNGR) (IFNGR)

The Interferon-gamma receptor (IFNGR) is a critical cell-surface heteromeric complex composed of two subunits, IFNGR1 and IFNGR2, which mediates the biological effects of Interferon-gamma (IFN-γ) [UniProt: P15260]. It is primarily expressed on immune cells, including macrophages, T cells, and B cells, where it triggers the JAK-STAT signaling pathway upon ligand binding [PubMed: 10648115]. This signaling is essential for activating macrophages, enhancing antigen presentation via MHC class I and II molecules, and promoting Th1-type immune responses [StatPearls: NBK541038]. Dysregulation of IFNGR signaling is linked to various pathologies; deficiency leads to Mendelian Susceptibility to Mycobacterial Disease (MSMD), while overactivity is a hallmark of Hemophagocytic Lymphohistiocytosis (HLH) [NIH: MSMD]. Therapeutic strategies include the use of recombinant IFN-γ (Interferon gamma-1b) to boost immune response in chronic granulomatous disease and monoclonal antibodies like emapalumab to neutralize excess IFN-γ in hyperinflammatory states [FDA: Gamifant]. The receptor's role in cancer is complex, as it can promote anti-tumor immunity but also contribute to immune evasion through the induction of PD-L1 [PubMed: 28978424]. Monitoring of IFNGR activity often involves measuring downstream chemokines like CXCL9 and CXCL10 [PubMed: 29103910].

Other names

IFN-gamma receptorCD119Interferon gamma receptor complexIFNGR1IFNGR2IFNGR

The receptor functions as a heterodimer that, upon binding its ligand (IFN-gamma), recruits JAK1 and JAK2 kinases to phosphorylate STAT1, leading to its nuclear translocation and gene transcription. Drugs like Interferon gamma-1b act as agonists to stimulate this pathway, while emapalumab neutralizes the ligand to prevent receptor activation.