IL17 is a highly versatile proinflammatory cytokine that is required for important physiological activities such as host immune defense, tissue repair, pathogenesis of inflammatory diseases and cancer progression.

(Data source: Beringer A, et al. Nat Rev Rheumatol. 2019)

IL17 composition:

The IL17 family includes six members (IL17A to IL17F), whose biological functions are mediated by IL17 receptors (IL17RA to IL17RE). The most studied is IL17A (also known as cytotoxic T lymphocyte-associated antigen 8, CTLA8), which, like IL17F, promotes its biological activity by binding to IL17RA and IL17RC.

(Data source: Amatya N , et al. Trends Immunol. 2017)

IL17 related structures:

All IL17 receptor subunits are single-pass transmembrane chains with unique properties, primarily composed of three domains: fibronectin (FN) 1, FN2, and SEFIR. The intracellular fragment of IL17RA also contains a Toll/IL-1 receptor (TIR)-like loop domain and a CCAAT/enhancer binding protein-β (C/EBPβ) activation domain (CBAD). Different receptor subunits assemble into heterodimers on the cell membrane, binding to ligands for signal transduction. IL17A and IL17F primarily activate downstream signaling pathways through IL17RA and IL17RC heterodimers. The three similar IL17 dimers differ in their ability to bind to IL17R: IL17A/A > IL17A/F > IL17F/F.

(Data source Blythe EN, et al. Front Immunol. 2021)

IL17 signaling pathway and regulation:

The IL17-mediated signaling pathway shares some similarities and differences with the Toll-like receptor (TLR)/IL-1R signaling pathway. Transcriptional regulation: IL17 binds to its heterodimeric receptor, and Act1 binds to TRAF6 to activate the NF-κB and MAPK pathways, promoting the onset and progression of inflammation. Post-transcriptional regulation: The Act1-TRAF2-TRAF5 complex binds to its receptor, activating downstream signaling pathways that mediate mRNA stabilization and translation of IL17 target genes.

(Data source: Huangfu L, et al. Signal Transduct Target Ther. 2023)

Clinical value of IL17:

IL17 plays an important role in protective immunity and immunopathology: it binds to pattern recognition receptors (PRRs) and activates innate immune cells; in autoimmune diseases (or infection-induced immunopathology), it stimulates the production of chemokines, recruits neutrophils and macrophages, and promotes inflammation.

(Data source: Mills KHG. Nat Rev Immunol. 2023)

Imbalance of IL17 may lead to autoimmune diseases and tissue destruction. Excessive levels of IL17 in the body are associated with the occurrence and exacerbation of multiple autoimmune diseases. Many antibody drugs targeting the IL17 signaling pathway have been approved for clinical use, mainly for inflammatory skin diseases.