miR-99a regulates CD4(+) T cell differentiation and attenuates experimental autoimmune encephalomyelitis by mTOR-mediated glycolysis.
miR-99a regulates CD4(+) T cell differentiation and attenuates experimental autoimmune encephalomyelitis by mTOR-mediated glycolysis.
复制标题
miR-99a 通过 mTOR 介导的糖酵解调节 CD4 T 细胞分化并减轻实验性自身免疫性脑脊髓炎
DOI：
10.1016/j.omtn.2021.07.010
复制
发表时间：
2021-12-03
期刊：
影响因子：
--
通讯作者：
Lu E
中科院分区：
文献类型：
--
作者：
Gu Y;Zhou H;Yu H;Yang W;Wang B;Qian F;Cheng Y;He S;Zhao X;Zhu L;Zhang Y;Jin M;Lu E
多种microrna在调节炎症和自身免疫性疾病中表现出不同的功能。MicroRNA-99a （miR-99a）已被证明参与脂肪组织炎症，并在自身免疫性疾病类风湿性关节炎和系统性红斑狼疮的炎症病变中下调。在这项研究中，我们发现miR-99a在实验性自身免疫性脑脊髓炎（EAE）小鼠（多发性硬化症动物模型）的CD4+ T细胞中下调。过表达miR-99a通过促进调节性T细胞和抑制辅助性T细胞1 （Th1）分化来缓解EAE的发展。生物信息学和功能分析进一步揭示了miR-99a的抗炎作用可归因于其通过靶向mTOR途径负性调节CD4+ T细胞糖酵解重编程。此外，通过转化生长因子β (TGF-β)诱导miR-99a表达，调节CD4+ T细胞糖酵解和分化。综上所述，我们的研究结果表征了miR-99a在EAE发展过程中调节CD4+ T细胞分化和糖酵解重编程中的关键作用，这可能表明miR-99a是改善多发性硬化症和其他自身免疫性疾病的有希望的治疗靶点。miR-99a促进Treg，抑制Th1细胞分化，缓解EAE的发展，这可归因于其负调控mtor依赖性糖酵解的作用。目前的研究表明miR-99a在EAE发展过程中调节CD4+ T细胞分化的关键作用，代表了一种有希望的EAE治疗方法。
Multiple microRNAs exhibit diverse functions to regulate inflammatory and autoimmune diseases. MicroRNA-99a (miR-99a) has been shown to be involved in adipose tissue inflammation and to be downregulated in the inflammatory lesions of autoimmune diseases rheumatoid arthritis and systemic lupus erythematosus. In this study, we found that miR-99a was downregulated in CD4+ T cells from experimental autoimmune encephalomyelitis (EAE) mice, an animal model of multiple sclerosis. Overexpression of miR-99a alleviated EAE development by promoting regulator T cells and inhibiting T helper type 1 (Th1) cell differentiation. Bioinformatics and functional analyses further revealed that the anti-inflammatory effects of miR-99a was attributable to its role in negatively regulating glycolysis reprogramming of CD4+ T cells by targeting the mTOR pathway. Additionally, miR-99a expression was induced by transforming growth factor β (TGF-β) to regulate CD4+ T cell glycolysis and differentiation. Taken together, our results characterize a pivotal role of miR-99a in regulating CD4+ T cell differentiation and glycolysis reprogramming during EAE development, which may indicate that miR-99a is a promising therapeutic target for the amelioration of multiple sclerosis and possibly other autoimmune diseases. miR-99a promotes Treg and inhibits Th1 cell differentiation to alleviate EAE development, which is attributable to its role in negatively regulating mTOR-dependent glycolysis. The current study characterizes a pivotal role of miR-99a in regulating CD4+ T cell differentiation during EAE development and represents a promising therapeutic approach for EAE.
登录
查看更多内容
影响因子：
32.4
作者：
O'Connell RM;Kahn D;Gibson WS;Round JL;Scholz RL;Chaudhuri AA;Kahn ME;Rao DS;Baltimore D
通讯作者：
Baltimore D
影响因子：
30.5
作者：
Du, Changsheng;Liu, Chang;Pei, Gang
通讯作者：
Pei, Gang
影响因子：
6.1
作者：
Han, Zhiyang;Guan, Yinghui;Jing, Bao
通讯作者：
Jing, Bao
影响因子：
5.5
作者：
Salmond RJ
通讯作者：
Salmond RJ
影响因子：
12.7
作者：
Cantoni C;Cignarella F;Ghezzi L;Mikesell B;Bollman B;Berrien-Elliott MM;Ireland AR;Fehniger TA;Wu GF;Piccio L
通讯作者：
Piccio L