Tumor necrosis factor receptor 1 and 2 (TNFR1 and TNFR2)

Tumor necrosis factor receptor 1 and tumor necrosis factor receptor 2 are members of the tumor necrosis factor receptor superfamily, functioning as cell surface transmembrane receptors that interact with the pro-inflammatory cytokine TNFα. TNFR1 contains a death domain on its cytoplasmic tail, which allows it to activate apoptotic and necroptotic pathways, as well as promote survival and activation through NF-κB and MAP kinase signaling. TNFR2 lacks a death domain and is more involved in immune regulation, cell survival, and proliferation, typically in cells of hematopoietic or immune origin. Both receptors are central in the pathogenesis and treatment of chronic inflammation, autoimmune disease, cancer, and infection due to their pleiotropic effects, making them widely studied therapeutic targets in clinical medicine. Drugs that target these receptors, by blocking TNFα or modulating receptor function directly, are established components of treatment for rheumatoid arthritis, inflammatory bowel disease, and several other disorders. Serum receptor levels and receptor mutations are used as biomarkers for patient stratification, therapeutic monitoring, and risk assessment in genetic and acquired diseases.

Other names

TNFRSF1ACD120aTumor necrosis factor receptor superfamily member 1ATNFRSF1BCD120b

Competitive inhibition (by blocking TNFα binding); Allosteric modulation (changing receptor conformational states and activation); Decoy receptor (“trap” TNF—a mechanism used by fusion proteins like etanercept); Inhibition of downstream NF-κB or apoptotic pathway activation.