Tumor necrosis factor (TNF) signaling pathway (TNF signaling pathway)

The Tumor necrosis factor (TNF) signaling pathway is a central regulator of the mammalian immune system and a key driver of inflammatory responses (StatPearls: TNF Inhibitors, 2023). It is activated by the binding of the cytokine TNF (specifically TNF-alpha) to two distinct cell-surface receptors: Tumor necrosis factor receptor 1 (TNFR1) and Tumor necrosis factor receptor 2 (TNFR2) (UniProt: P01375, P19438). This interaction triggers intracellular signaling cascades, including the NF-kappaB and MAPK pathways, which govern cell survival, proliferation, and the production of pro-inflammatory cytokines (KEGG: hsa04668). Conversely, under specific conditions, the pathway can induce programmed cell death via apoptosis or necroptosis (Nature Reviews Molecular Cell Biology, 2012). Dysregulation of TNF signaling is implicated in the pathogenesis of numerous autoimmune and inflammatory disorders, such as rheumatoid arthritis, Crohn's disease, and plaque psoriasis (PubMed: 28545184). Therapeutic strategies targeting this pathway primarily involve monoclonal antibodies or soluble receptor fusion proteins that neutralize TNF-alpha, thereby preventing receptor activation and dampening systemic inflammation (FDA: Remicade Prescribing Information). However, long-term inhibition of this pathway is associated with significant safety risks, including an increased susceptibility to opportunistic infections like tuberculosis and a potential risk of malignancy (StatPearls: TNF Inhibitors, 2023).

Other names

TNF-TNFR signaling pathwayTumor necrosis factor-alpha signaling pathwayTNF-mediated signaling

Neutralization of soluble and membrane-bound tumor necrosis factor-alpha (TNF-alpha), preventing its interaction with TNFR1 and TNFR2 receptors.