Cardiac myosin-Th17 responses promote heart failure in human myocarditis

摘要: In human myocarditis and its sequela dilated cardiomyopathy (DCM), the mechanisms immune phenotype governing disease subsequent heart failure are not known. Here, we identified a Th17 cell immunophenotype of myocarditis/DCM with elevated CD4+IL17+ T cells Th17-promoting cytokines IL-6, TGF-β, IL-23 as well GM-CSF-secreting CD4+ cells. The was linked effects cardiac myosin on CD14+ monocytes, TLR2, failure. Persistent associated high percentages IL-17-producing IL-17-promoting cytokines, included significantly low FOXP3+ Tregs, which may contribute to severity. We demonstrate potentially novel mechanism in TLR2 peptide ligands from stimulated exaggerated Th17-related including myocarditic monocytes vitro, an anti-TLR2 antibody abrogated cytokine response. Our translational study explains how be initiated by TLR ligand stimulation generate development pathogenic failure, provides rationale for targeting IL-17A therapeutic option.