Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) (TNFR1)

Tumor necrosis factor receptor superfamily member 1A (TNFR1) is a ubiquitous membrane receptor that serves as a primary mediator of the biological effects of tumor necrosis factor-alpha (TNF-α) [1, 5]. It is characterized by an intracellular death domain (DD) that allows it to trigger both pro-inflammatory signaling via NF-κB and programmed cell death pathways, including apoptosis and necroptosis [2, 3, 9]. Dysregulation of TNFR1 signaling is a hallmark of numerous chronic inflammatory and autoimmune diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease [3, 7, 14]. While traditional anti-TNF therapies like infliximab and adalimumab neutralize the ligand to prevent receptor activation, newer therapeutic strategies focus on selective TNFR1 antagonism to preserve the tissue-protective and immunomodulatory functions of TNFR2 [7, 8, 14]. Additionally, soluble TNFR1 (sTNFR1) has emerged as a significant biomarker for predicting disease severity and mortality in conditions like diabetic kidney disease and COVID-19 [18, 20].

Other names

CD120ap55p60TNF-R1TNF-RITNFR-ITNF-R55TNF-R60Tumor necrosis factor receptor 1Tumor necrosis factor receptor type I

Direct antagonism of TNFR1 to block TNF-alpha binding and downstream pro-inflammatory/apoptotic signaling, or neutralization of the TNF-alpha ligand to prevent its interaction with the receptor [3, 7, 11].