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To address this question, we utilized complimentary studies to determine responsiveness of human normal and pathogenic lung fibroblasts to IL-17A and used lung biopsies acquired from patients with IPF and RA-ILD to determine IL-17A receptor (IL-17RA) expression. Both normal and pathogenic IPF lung fibroblasts express functional IL-17RA and respond to IL-17A stimulation with cell proliferation, generation of extracellular matrix (ECM) proteins, and induction of myofibroblast transdifferentiation. Small interfering RNA (siRNA) silencing of IL-17RA attenuated this fibroblast response to IL-17A on ECM production. These fibroblast responses to IL-17A are dependent on NF-\u03baB-mediated signaling. In addition, inhibiting Janus activated kinase (JAK) 2 by either siRNA or a selective pharmacological inhibitor, AZD1480\u2014but not a JAK1\/JAK3 selective inhibitor, tofacitinib\u2014also significantly reduced this IL-17A-induced fibrogenic response. Lung biopsies of RA-ILD patients demonstrate significantly higher IL-17RA expression in areas of fibroblast accumulation and fibrosis, compared with either IPF or normal lung tissue. These observations support a direct role for IL-17A in lung fibrosis that may be particularly relevant in the context of RA-ILD.<\/jats:p>","DOI":"10.1152\/ajplung.00301.2018","type":"journal-article","created":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T07:14:52Z","timestamp":1546499692000},"page":"L487-L497","source":"Crossref","is-referenced-by-count":181,"title":["Profibrotic effect of IL-17A and elevated IL-17RA in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated lung disease support a direct role for IL-17A\/IL-17RA in human fibrotic interstitial lung disease"],"prefix":"10.1152","volume":"316","author":[{"given":"Jie","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota"},{"name":"Division of Pulmonary Medicine, Department of Medicine, Chongqing General Hospital, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine, Guang\u2019anmen Hospital, China Academy of Chinese Medicine Science, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja C.","family":"Roden","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Emergency, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujuan","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota"},{"name":"Division of Endocrinology, Department of Medicine, First Affiliated Hospital of Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2968-224X","authenticated-orcid":false,"given":"Y. 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