A comprehensive network map of IL-17A signaling pathway

• Published in: Journal of cell communication and signaling Vol. 17; no. 1; pp. 209 - 215
• Main Authors: Rex, D. A. B., Dagamajalu, Shobha, Gouda, Mahesh Manjunath, Suchitha, G. P., Chanderasekaran, Jaikanth, Raju, Rajesh, Prasad, T. S. Keshava, Bhandary, Yashodhar Prabhakar
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.03.2023; John Wiley & Sons, Inc
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Autoimmune diseases; Biomedical and Life Sciences; Biomedicine; Bleomycin; Catalysis; Cell Biology; Chemokines; Cytokines; Fibrosis; Gene regulation; Helper cells; Inflammation; Interleukin 17; Interleukin 6; Interleukin 8; Kinases; Leukocytes (neutrophilic); Life Sciences; Lung diseases; Lung injury; Lymphocytes T; NF-κB protein; Nuts and Bolts; Protein transport; Protein-serine/threonine kinase; Proteins; Protein–protein interactions; Rapamycin; Respiratory tract diseases; Signal transduction; Signaling pathways; TOR protein; Signaling pathways; Bleomycin; Protein–protein interactions; Cytokines; Fibrosis; Inflammation; Lung injury
• ISSN: 1873-9601; 1873-961X
• DOI: 10.1007/s12079-022-00686-y

Interleukin-17A (IL-17A) is one of the member of IL-17 family consisting of other five members (IL-17B to IL-17F). The Gamma delta (γδ) T cells and T helper 17 (Th17) cells are the major producers of IL-17A. Aberrant signaling by IL-17A has been implicated in the pathogenesis of several autoimmune diseases including idiopathic pulmonary fibrosis, acute lung injury, chronic airway diseases, and cancer. Activation of the IL-17A/IL-17 receptor A (IL-17RA) system regulates phosphoinositide 3-kinase/AKT serine/threonine kinase/mammalian target of rapamycin (PI3K/AKT/mTOR), mitogen-activated protein kinases (MAPKs) and activation of nuclear factor-κB (NF-κB) mediated signaling pathways. The IL-17RA activation orchestrates multiple downstream signaling cascades resulting in the release of pro-inflammatory cytokines such as interleukins (IL)-1β, IL-6, and IL-8, chemokines (C-X-C motif) and promotes neutrophil-mediated immune response. Considering the biomedical importance of IL-17A, we developed a pathway resource of signaling events mediated by IL-17A/IL-17RA in this study. The curation of literature data pertaining to the IL-17A system was performed manually by the NetPath criteria. Using data mined from the published literature, we describe an integrated pathway reaction map of IL-17A/IL-17RA consisting of 114 proteins and 68 reactions. That includes detailed information on IL-17A/IL-17RA mediated signaling events of 9 activation/inhibition events, 17 catalysis events, 3 molecular association events, 68 gene regulation events, 109 protein expression events, and 6 protein translocation events. The IL-17A signaling pathway map data is made freely accessible through the WikiPathways Database ( https://www.wikipathways.org/index.php/Pathway : WP5242).