{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:28:36Z","timestamp":1792452516153,"version":"4.5.0"},"reference-count":88,"publisher":"American Society for Clinical Investigation","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,16]]},"abstract":"<jats:p>\n                    In human myocarditis and its sequela dilated cardiomyopathy (DCM), the mechanisms and immune phenotype governing disease and subsequent heart failure are not known. Here, we identified a Th17 cell immunophenotype of human myocarditis\/DCM with elevated CD4\n                    <jats:sup>+<\/jats:sup>\n                    IL17\n                    <jats:sup>+<\/jats:sup>\n                    T cells and Th17-promoting cytokines IL-6, TGF-\u03b2, and IL-23 as well as GM-CSF\u2013secreting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. The Th17 phenotype was linked with the effects of cardiac myosin on CD14\n                    <jats:sup>+<\/jats:sup>\n                    monocytes, TLR2, and heart failure. Persistent heart failure was associated with high percentages of IL-17\u2013producing T cells and IL-17\u2013promoting cytokines, and the myocarditis\/DCM phenotype included significantly low percentages of FOXP3\n                    <jats:sup>+<\/jats:sup>\n                    Tregs, which may contribute to disease severity. We demonstrate a potentially novel mechanism in human myocarditis\/DCM in which TLR2 peptide ligands from human cardiac myosin stimulated exaggerated Th17-related cytokines including TGF-\u03b2, IL-6, and IL-23 from myocarditic CD14\n                    <jats:sup>+<\/jats:sup>\n                    monocytes in vitro, and an anti-TLR2 antibody abrogated the cytokine response. Our translational study explains how an immune phenotype may be initiated by cardiac myosin TLR ligand stimulation of monocytes to generate Th17-promoting cytokines and development of pathogenic Th17 cells in human myocarditis and heart failure, and provides a rationale for targeting IL-17A as a therapeutic option.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.85851","type":"journal-article","created":{"date-parts":[[2016,6,15]],"date-time":"2016-06-15T14:17:40Z","timestamp":1466000260000},"source":"Crossref","is-referenced-by-count":227,"title":["Cardiac myosin-Th17 responses promote heart failure in human myocarditis"],"prefix":"10.1172","volume":"1","author":[{"given":"Jennifer M.","family":"Myers","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie T.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, Mayo Clinic, Jacksonville, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Kem","sequence":"additional","affiliation":[{"name":"Department of Medicine\/Endocrinology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stavros","family":"Stavrakis","sequence":"additional","affiliation":[{"name":"Medicine\/Cardiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley D.","family":"Kosanke","sequence":"additional","affiliation":[{"name":"Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan M.","family":"Shevach","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DeLisa","family":"Fairweather","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, Mayo Clinic, Jacksonville, Florida, USA."},{"name":"Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Stoner","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol J.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine W.","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2016,6,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.3225"},{"issue":"8","key":"B2","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.4049\/jimmunol.138.8.2488","article-title":"Autoantibodies specific for the cardiac myosin isoform are found in mice susceptible to coxsackievirus B3 induced myocarditis","volume":"138","author":"Neu","year":"1987","journal-title":"J Immunol"},{"issue":"55","key":"B3","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/3-540-30822-9_11","article-title":"Clinical implications of anti-cardiac immunity in dilated cardiomyopathy","author":"Caforio","year":"2006","journal-title":"Ernst Schering Res Found Workshop"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0800861"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/08916930802031579"},{"key":"B6","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0065-3527(08)60783-6","article-title":"Enteroviruses and myocarditis: viral pathogenesis through replication, cytokine induction, and immunopathogenicity","volume":"51","author":"Huber","year":"1998","journal-title":"Adv Virus Res"},{"key":"B7"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0800028"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-012-9358-3"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2012-301686"},{"issue":"1","key":"B11","first-page":"3","article-title":"Myocarditis. 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