IFNGR

IFNGR, short for the interferon gamma receptor, is a cell-surface receptor that binds the cytokine interferon-gamma (IFN-γ). It functions as a heterodimer composed of two subunits, IFNGR1 and IFNGR2. Binding of IFN-γ to IFNGR1 promotes the formation of the receptor complex with IFNGR2 and initiates intracellular signaling.

IFNGR1 is primarily involved in ligand binding and receptor assembly, while IFNGR2 participates in transmitting the signal into the cell. The receptor belongs to the class II cytokine receptor family. Upon IFN-γ engagement, receptor-associated Janus kinases JAK1 and JAK2 become activated, leading to phosphorylation of the transcription factor STAT1. Phosphorylated STAT1 dimerizes and translocates to the nucleus, where it drives the expression of interferon-stimulated genes that mediate immune and antimicrobial responses.

The IFN-γ signaling axis plays a central role in activating macrophages, enhancing phagocytosis, promoting antigen presentation through upregulation of MHC class I and II molecules, and boosting microbicidal mechanisms such as nitric oxide production. These effects support defense against intracellular pathogens, particularly mycobacteria, Salmonella, and Listeria species. IFNGR signaling is tightly regulated by negative feedback mechanisms, including SOCS proteins, receptor internalization, and transcriptional control of pathway components.

Clinical relevance includes genetic defects in IFNGR1 or IFNGR2 that cause impaired IFN-γ signaling, leading to increased susceptibility to mycobacterial and other intracellular infections (Mendelian susceptibility to mycobacterial disease). Therapeutically, recombinant IFN-γ has been used to augment immune function in certain primary immune deficiencies and chronic granulomatous disease.