• Exp. Cell Res. · Feb 2019

    PPARα suppresses Th17 cell differentiation through IL-6/STAT3/RORγt pathway in experimental autoimmune myocarditis.

    • He Chang, Fayun Zhao, Xinwen Xie, Yanchun Liao, Ying Song, Chunxiao Liu, Yang Wu, Yue Wang, Donghui Liu, Yan Wang, Jun Zou, and Zhi Qi.
    • Medical College of Xiamen University, Xiamen 361102, China; Xiamen Cardiovascular Hospital of Xiamen University, Xiamen 361004, China; Department of Geriatrics, Xiang'an Hospital of Xiamen University, Xiamen 361000, China. Electronic address: changhe@xmu.edu.cn.
    • Exp. Cell Res. 2019 Feb 1; 375 (1): 22-30.

    AbstractFamily members of peroxisome proliferator-activated receptors (PPARs), such as PPARγ, have been shown to be effective in regulating T helper 17 (Th17) cell differentiation. However, whether PPARα, another important family member of PPARs, contributes to Th17 cell differentiation remains controversial. In the present study, we show that PPARα may be a negative regulator of Th17 cell differentiation. In CD4+ T cells from PPARα knockout mice, PPARα deficiency enhances IL-17 and IL-6 levels and promotes Th17 cell differentiation. In contrast, in CD4+ T cells from wild type mice, PPARα activation suppresses Th17 cell differentiation. Furthermore, IL-6 neutralizing antibody dose-dependently reduces the activity of STAT3 and down-regulates the protein expression of RORγt in CD4+ T cells from PPARα knockout mice but has no effect on that of wild type mice. On the other hand, in isolated CD4+ T cells from experimental autoimmune myocarditis (EAM) rats, PPARα agonist Fenofibrate decreased the expression of IL-17 and RORγt, increased the expression of Foxp3, while PPARα antagonist MK886 reversed these effects. Importantly, in vivo activation of PPARα ameliorates EAM by suppressing Th17 cell differentiation through reducing the expression of RORγt and phosphorylated STAT3 that are upregulated in EAM hearts. These results imply that PPARα suppresses Th17 cell differentiation through IL-6/STAT3/RORγt signaling pathway and suggest that PPARα may become a molecular target for treating autoimmune myocarditis.Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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