Tumor necrosis factor and Interleukin-17 inflammatory signaling pathways (TNF/IL-17 pathways)

The Tumor necrosis factor (TNF) and Interleukin-17 (IL-17) inflammatory signaling pathways are interconnected biological networks that play a central role in the pathogenesis of various autoimmune and inflammatory disorders (PubMed: 31015715). TNF is a potent pro-inflammatory cytokine that regulates immune cell activation and programmed cell death, while IL-17, primarily secreted by Th17 cells, is crucial for host defense against extracellular pathogens but also drives chronic tissue inflammation (UniProt: P01375, Q16552). These two pathways often act synergistically; for instance, IL-17 can enhance the inflammatory effects of TNF by stabilizing mRNA of pro-inflammatory genes, leading to a massive production of chemokines and cytokines (PubMed: 21844396). This cooperative interaction is particularly evident in the skin and joints, contributing to the clinical manifestations of psoriasis and rheumatoid arthritis (StatPearls: NBK470458). Pharmacological intervention targeting these pathways, through the use of monoclonal antibodies or receptor fusion proteins, has revolutionized the treatment of these conditions by effectively reducing systemic and local inflammation (NIH: PMC6363012).

Other names

TNF-alpha and IL-17 signaling axisTNF/IL-17 synergistic pathwayPro-inflammatory cytokine signaling network

Neutralization of soluble and membrane-bound pro-inflammatory cytokines (TNF-alpha, IL-17A, IL-17F) or blockade of their respective receptors to inhibit downstream intracellular signaling cascades such as NF-kappaB and MAPK pathways (PubMed: 21844396).