下调的 miR-374c 和 Hsp70 通过诱导实验性自身免疫性脑脊髓炎中的 Fas 表达促进 Th17 细胞分化。
Down-regulated miR-374c and Hsp70 promote Th17 cell differentiation by inducing Fas expression in experimental autoimmune encephalomyelitis.
机构信息
Department the Second Clinical Medical College, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
The College of Basic Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
出版信息
Int J Biol Macromol. 2020 Jul 1;154:1158-1165. doi: 10.1016/j.ijbiomac.2019.11.147. Epub 2019 Nov 19.
OBJECTIVE
Fas is a positive regulator of Th17 cells differentiation in experimental autoimmune encephalomyelitis (EAE). However, its upstream regulators are still not fully determined. This study was designed to explore the upstream regulators of Fas in regulating Th17 cells differentiation in EAE.
METHODS
The mouse model of EAE was established by myelin oligodendrocyte glycoprotein injection. Th17 cells differentiation was induced by IL-23, IL-6 and TGF-β.
RESULTS
Down-regulated Hsp70 and miR-374c and up-regulated Fas were observed in the spleen and brain of EAE mice. Hsp70 overexpression evidently reduced Fas protein level, but not mRNA level. The luciferase reporter assay indicated that miR-374c targets Fas. Overexpression of miR-374c down-regulated the mRNA and protein level of Fas. The concentration of IL-17A in CD4+ T-cells was reduced by miR-374c or Hsp70 overexpression, and Fas overexpression altered this trend. Hsp70 did not regulate the expression of miR-374c, and likewise, miR-374c did not regulate the expression of Hsp70. Further results suggested that Hsp70 and miR-374c regulated Fas expression through different ways to affect Th17 cells differentiation in EAE.
CONCLUSIONS
This study suggested that down-regulated miR-374c and Hsp70 promote Th17 cell differentiation by inducing Fas expression in EAE.
目的
Fas 是实验性自身免疫性脑脊髓炎（EAE）中 Th17 细胞分化的正向调节因子。然而，其上游调节因子尚未完全确定。本研究旨在探讨 Fas 的上游调节因子在调节 EAE 中 Th17 细胞分化中的作用。
方法
通过髓鞘少突胶质细胞糖蛋白注射建立 EAE 小鼠模型。通过 IL-23、IL-6 和 TGF-β诱导 Th17 细胞分化。
结果
在 EAE 小鼠的脾脏和大脑中观察到 Hsp70、miR-374c 和 Fas 的表达下调。Hsp70 的过表达明显降低了 Fas 蛋白水平，但不影响 Fas mRNA 水平。荧光素酶报告基因检测表明 miR-374c 靶向 Fas。miR-374c 的过表达下调了 Fas 的 mRNA 和蛋白水平。miR-374c 或 Hsp70 的过表达降低了 CD4+T 细胞中 IL-17A 的浓度，并改变了 Fas 的过表达趋势。Hsp70 不调节 miR-374c 的表达，反之亦然，miR-374c 也不调节 Hsp70 的表达。进一步的研究结果表明，Hsp70 和 miR-374c 通过不同的方式调节 Fas 表达，从而影响 EAE 中的 Th17 细胞分化。
结论
本研究表明，下调的 miR-374c 和 Hsp70 通过诱导 Fas 表达促进 EAE 中 Th17 细胞分化。
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