miR-99a regulates CD4+ T cell differentiation and attenuates experimental autoimmune encephalomyelitis by mTOR-mediated glycolysis

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 erythe...

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Autores principales:	Yuting Gu, Hong Zhou, Hongshuang Yu, Wanlin Yang, Bei Wang, Fengtao Qian, Yiji Cheng, Shan He, Xiaonan Zhao, Linqiao Zhu, Yanyun Zhang, Min Jin, Eryi Lu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	miR-99a EAE T-cell differentiation glycolysis mTOR TGF-β Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/a26ed6a4d7f84c5fbba9381bc37c6c1a
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spelling	oai:doaj.org-article:a26ed6a4d7f84c5fbba9381bc37c6c1a2021-11-14T04:32:25ZmiR-99a regulates CD4+ T cell differentiation and attenuates experimental autoimmune encephalomyelitis by mTOR-mediated glycolysis2162-253110.1016/j.omtn.2021.07.010https://doaj.org/article/a26ed6a4d7f84c5fbba9381bc37c6c1a2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2162253121001785https://doaj.org/toc/2162-2531Multiple 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.Yuting GuHong ZhouHongshuang YuWanlin YangBei WangFengtao QianYiji ChengShan HeXiaonan ZhaoLinqiao ZhuYanyun ZhangMin JinEryi LuElsevierarticlemiR-99aEAET-cell differentiationglycolysismTORTGF-βTherapeutics. PharmacologyRM1-950ENMolecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 1173-1185 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	miR-99a EAE T-cell differentiation glycolysis mTOR TGF-β Therapeutics. Pharmacology RM1-950
spellingShingle	miR-99a EAE T-cell differentiation glycolysis mTOR TGF-β Therapeutics. Pharmacology RM1-950 Yuting Gu Hong Zhou Hongshuang Yu Wanlin Yang Bei Wang Fengtao Qian Yiji Cheng Shan He Xiaonan Zhao Linqiao Zhu Yanyun Zhang Min Jin Eryi Lu miR-99a regulates CD4+ T cell differentiation and attenuates experimental autoimmune encephalomyelitis by mTOR-mediated glycolysis
description	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.
format	article
author	Yuting Gu Hong Zhou Hongshuang Yu Wanlin Yang Bei Wang Fengtao Qian Yiji Cheng Shan He Xiaonan Zhao Linqiao Zhu Yanyun Zhang Min Jin Eryi Lu
author_facet	Yuting Gu Hong Zhou Hongshuang Yu Wanlin Yang Bei Wang Fengtao Qian Yiji Cheng Shan He Xiaonan Zhao Linqiao Zhu Yanyun Zhang Min Jin Eryi Lu
author_sort	Yuting Gu
title	miR-99a regulates CD4+ T cell differentiation and attenuates experimental autoimmune encephalomyelitis by mTOR-mediated glycolysis
title_short	miR-99a regulates CD4+ T cell differentiation and attenuates experimental autoimmune encephalomyelitis by mTOR-mediated glycolysis
title_full	miR-99a regulates CD4+ T cell differentiation and attenuates experimental autoimmune encephalomyelitis by mTOR-mediated glycolysis
title_fullStr	miR-99a regulates CD4+ T cell differentiation and attenuates experimental autoimmune encephalomyelitis by mTOR-mediated glycolysis
title_full_unstemmed	miR-99a regulates CD4+ T cell differentiation and attenuates experimental autoimmune encephalomyelitis by mTOR-mediated glycolysis
title_sort	mir-99a regulates cd4+ t cell differentiation and attenuates experimental autoimmune encephalomyelitis by mtor-mediated glycolysis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/a26ed6a4d7f84c5fbba9381bc37c6c1a
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miR-99a regulates CD4+ T cell differentiation and attenuates experimental autoimmune encephalomyelitis by mTOR-mediated glycolysis

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