| First Author | Chang H | Year | 2019 |
| Journal | Exp Cell Res | Volume | 375 |
| Issue | 1 | Pages | 22-30 |
| PubMed ID | 30557558 | Mgi Jnum | J:272838 |
| Mgi Id | MGI:6281783 | Doi | 10.1016/j.yexcr.2018.12.005 |
| Citation | Chang H, et al. (2019) PPARalpha suppresses Th17 cell differentiation through IL-6/STAT3/RORgammat pathway in experimental autoimmune myocarditis. Exp Cell Res 375(1):22-30 |
| abstractText | Family members of peroxisome proliferator-activated receptors (PPARs), such as PPARgamma, have been shown to be effective in regulating T helper 17 (Th17) cell differentiation. However, whether PPARalpha, another important family member of PPARs, contributes to Th17 cell differentiation remains controversial. In the present study, we show that PPARalpha may be a negative regulator of Th17 cell differentiation. In CD4(+) T cells from PPARalpha knockout mice, PPARalpha deficiency enhances IL-17 and IL-6 levels and promotes Th17 cell differentiation. In contrast, in CD4(+) T cells from wild type mice, PPARalpha activation suppresses Th17 cell differentiation. Furthermore, IL-6 neutralizing antibody dose-dependently reduces the activity of STAT3 and down-regulates the protein expression of RORgammat in CD4(+) T cells from PPARalpha 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, PPARalpha agonist Fenofibrate decreased the expression of IL-17 and RORgammat, increased the expression of Foxp3, while PPARalpha antagonist MK886 reversed these effects. Importantly, in vivo activation of PPARalpha ameliorates EAM by suppressing Th17 cell differentiation through reducing the expression of RORgammat and phosphorylated STAT3 that are upregulated in EAM hearts. These results imply that PPARalpha suppresses Th17 cell differentiation through IL-6/STAT3/RORgammat signaling pathway and suggest that PPARalpha may become a molecular target for treating autoimmune myocarditis. |
