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- W2619279036 abstract "Background: Chronic inflammation is closely associated with heart failure; however, the molecular and cellular mechanisms of inflammatory reactions remain to be fully elucidated. Interleukin(IL)-17 is a pro-inflammatory cytokine that is produced by Th17 cells. Th17 cells are induced by IL-6 and transforming growth factor(TGF-β), through up-regulation of its specific transcriptional factor, retinoic acid receptor-related orphan nuclear receptor(ROR)γt. Th17 cells are reported to participate in pathogenesis of chronic inflammatory disease. In this study, we examined the functional roles of Th17 signaling in cardiac inflammation using murine experimental autoimmune myocarditis(EAM) model. Methods and Results: EAM was induced in wild-type(WT) and/or RORγt-eGFP knock-in Balb/c mice by immunization twice with α-myosin heavy chain peptide. Three weeks after the first immunization, the mRNA expression of RORγt was up-regulated and correlated with the disease severity in heart. Additionally, in immunostaining and flow cytometry analysis, we observed a significant number of Th17 cells among inflammatory cells infiltrating myocardium from WT and RORγt-eGFP knock-in heterozygous mice. These data showed that Th17 cells were remarkably recruited in EAM heart. Moreover, depression of Th17 differentiation suppressed disease severity completely with inhibition of RORγt and IL-17 transcriptional activity, whereas IL-17 neutralizing antibody to lesser extent. Finally, RORγt-eGFP knock-in homozygous mice were protected from cardiac inflammation. Conclusion: Our results indicated that Th17 activation through RORγt pathway is a critical mechanism for the development of myocarditis. However, IL-17 is not crucial for induction of EAM, suggesting that other Th17 producing pro-inflammatory cytokines are involved. It could be proposed that Th17 cells are novel therapeutic target against chronic inflammation in heart." @default.
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- W2619279036 date "2011-12-09" @default.
- W2619279036 modified "2023-09-24" @default.
- W2619279036 title "Abstract P159: Th17 Cells Are Indispensable for Cardiac Inflammation in Autoimmune Myocarditis" @default.
- W2619279036 doi "https://doi.org/10.1161/res.109.suppl_1.ap159" @default.
- W2619279036 hasPublicationYear "2011" @default.
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