Abstract 14566: Th17 Cells Exhibit Protective Effects Against Cardiac Fibrosis After Myocardial Infarction
Background: Cardiac inflammation is closely associated with heart failure; however, the molecular and cellular mechanisms of inflammatory reactions in myocardium remain to be fully elucidated. Interleukin-17 (IL-17) producing helper T cells (Th17 cells) have been reported to participate in pathogenesis of chronic inflammation. Recently, we have reported that Th17 cells are essential for experimental autoimmune myocarditis. In this study, we examined the functional role of Th17 signaling in cardiac inflammation using murine myocardial infarction (MI) model.
Methods and Results: MI was generated by ligating the left coronary artery. Quantitative RT-PCR analysis showed that the cardiac expression of IL-17 mRNA started to increase 2 weeks after MI, while IL-6 mRNA was upregulated immediately after MI operation, suggesting that IL-17 could be a marker cytokine for chronic inflammation in post-infarct myocardium. Next, the infiltrating cells into post-infarct myocardium were prepared by collagenase digestion and characterized by staining with anti-IL-17 and -CD4 antibodies. Flow cytometric analysis showed that IL-17 producing CD4+ cells, designated as Th17 cells, were infiltrated in hearts 14 and 21 days after MI. Interestingly, the treatment with anti-IL-17 antibody failed to attenuate cardiac fibrosis after MI, indicating that IL-17 production is not critical for the chronic inflammation after MI. Since retinoic acid receptor-related orphan nuclear receptor (ROR) γt is responsible for the transdifferentiation from naïve T cell to Th17 cells, we examined the effect of ablation of RORγt in the hearts exposed to MI, using transgenic mice harboring eGFP cDNA at the 1st exon of RORγt gene. Surprisingly, histological analyses by Masson-Trichrome staining revealed that cardiac fibrosis was exacerbated in RORγt-null mice 14 days after MI, compared with control mice. In addition, the cardiac expression of IL-17 mRNA was completely eliminated in RORγt-null mice, indicating that Th17 cells were abolished in RORγt-null mice.
Conclusion: Th17 cells exhibited cardioprotective activities in post-infarct myocardium, attenuating cardiac fibrosis, as a novel function of Th17 cells.
- © 2011 by American Heart Association, Inc.