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

Tumor necrosis factor receptor 1 (TNFR1) and Tumor necrosis factor receptor 2 (TNFR2) are the primary cell surface receptors that mediate the biological effects of tumor necrosis factor-alpha (TNF-alpha), a potent cytokine involved in systemic inflammation. TNFR1, also known as p55 or CD120a, is constitutively expressed in most tissues and contains a cytoplasmic death domain that allows it to initiate both pro-inflammatory signaling via the NF-kappaB pathway and programmed cell death through apoptosis (UniProt P19438). In contrast, TNFR2, also known as p75 or CD120b, is primarily expressed on immune cells and endothelial cells, lacks a death domain, and typically promotes cell survival, proliferation, and tissue regeneration (UniProt P20333). Together, these receptors coordinate the body's response to infection and injury, but their chronic activation is a central driver of various autoimmune and inflammatory pathologies. In clinical medicine, these receptors are the ultimate targets of TNF-inhibitor therapy, which is used to treat conditions such as rheumatoid arthritis, psoriasis, and Crohn's disease (StatPearls, 2023). Drugs like etanercept act as soluble decoy receptors to sequester TNF-alpha, while monoclonal antibodies like adalimumab and infliximab prevent the cytokine from binding to TNFR1 and TNFR2 on the cell surface. While these therapies are highly effective at reducing inflammation, they carry significant safety risks, including an increased susceptibility to serious opportunistic infections like tuberculosis and a potential risk for developing certain malignancies or demyelinating disorders (PubMed, 2022). Emerging research is also focusing on receptor-specific antagonists, such as those targeting TNFR1 to reduce inflammation while sparing the regenerative functions of TNFR2.

Other names

TNFRSF1A and TNFRSF1BCD120a and CD120bp55 and p75TNF-R1 and TNF-R2Tumor necrosis factor receptor superfamily member 1ATumor necrosis factor receptor superfamily member 1B

Inhibition of tumor necrosis factor signaling through competitive binding of the ligand or direct receptor antagonism, preventing the activation of pro-inflammatory and apoptotic pathways.