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IL-21 primarily derived from Th17 cells promotes M2 macrophage polarization. Consistently, IL-21 receptor-deficient mice show resistance to HPH with no accumulation of M2 macrophages in the lungs. IL-21 and M2 macrophage markers were upregulated in the lungs of patients with end-stage idiopathic PAH. These findings suggest promising therapeutic strategies for PAH targeting IL-6\/IL-21\u2013signaling axis.<\/jats:p>","DOI":"10.1073\/pnas.1424774112","type":"journal-article","created":{"date-parts":[[2015,5,4]],"date-time":"2015-05-04T22:02:32Z","timestamp":1430776952000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":219,"title":["Interleukin-6\/interleukin-21 signaling axis is critical in the pathogenesis of pulmonary arterial hypertension"],"prefix":"10.1073","volume":"112","author":[{"given":"Takahiro","family":"Hashimoto-Kataoka","sequence":"first","affiliation":[{"name":"Departments of aCardiovascular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Hosen","sequence":"additional","affiliation":[{"name":"Cancer Stem Cell Biology Functional Diagnostic Science,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Sonobe","sequence":"additional","affiliation":[{"name":"Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, 565-8565, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoh","family":"Arita","sequence":"additional","affiliation":[{"name":"Departments of aCardiovascular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Yasui","sequence":"additional","affiliation":[{"name":"Departments of aCardiovascular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Masaki","sequence":"additional","affiliation":[{"name":"Departments of aCardiovascular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Minami","sequence":"additional","affiliation":[{"name":"General Thoracic Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadakatsu","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, 565-8565, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Cardiovascular Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Sawa","sequence":"additional","affiliation":[{"name":"Cardiovascular Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroimmunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, 060-0815, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kumanogoh","sequence":"additional","affiliation":[{"name":"Respiratory Medicine, Allergy and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Yamauchi-Takihara","sequence":"additional","affiliation":[{"name":"Departments of aCardiovascular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meinoshin","family":"Okumura","sequence":"additional","affiliation":[{"name":"General Thoracic Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadamitsu","family":"Kishimoto","sequence":"additional","affiliation":[{"name":"Laboratory of Immune Regulation, Immunology Frontier Research Center, Osaka University, Suita, Osaka, 565-0871, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issei","family":"Komuro","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, 113-8656, Japan; 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