Cardiac myosin-Th17 responses promote heart failure in human myocarditis

Jennifer M. Myers, Leslie T Jr. Cooper, David C. Kem, Stavros Stavrakis, Stanley D. Kosanke, Ethan M. Shevach, De Lisa Fairweather, Julie A. Stoner, Carol J. Cox, Madeleine W. Cunningham

Research output: Contribution to journalArticlepeer-review


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+IL17+ T cells and Th17-promoting cytokines IL-6, TGF-β, and IL-23 as well as GM-CSF–secreting CD4+ T cells. The Th17 phenotype was linked with the effects of cardiac myosin on CD14+ monocytes, TLR2, and heart failure. Persistent heart failure was associated with high percentages of IL-17–producing T cells and IL-17–promoting cytokines, and the myocarditis/DCM phenotype included significantly low percentages of FOXP3+ 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-β, IL-6, and IL-23 from myocarditic CD14+ 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.

Original languageEnglish (US)
Article numbere85851
JournalJCI Insight
Issue number9
StatePublished - Jun 16 2016

ASJC Scopus subject areas

  • Medicine(all)


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