MicroRNA-21 Regulates Diametrically Opposed Biological Functions of Regulatory T Cells

Regulatory T cells (Tregs) are considered important for controlling the onset and development of autoimmune disease. Although studies have shown that miR-21 is expressed at higher levels in Treg cells, it remains largely elusive whether miR-21 regulates the immune-suppressive function of Tregs. In t...

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Autores principales:	Jijun Sun, Ruiling Liu, Xiaozhen He, Jiang Bian, Wenbo Zhao, Weiyun Shi, Qingguo Ruan
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	miR-21 immune tolerance immune-regulation autoimmune disease regulatory T cell Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/cfadb639ae56419a8365902fee7f7c14
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spelling	oai:doaj.org-article:cfadb639ae56419a8365902fee7f7c142021-11-11T10:23:48ZMicroRNA-21 Regulates Diametrically Opposed Biological Functions of Regulatory T Cells1664-322410.3389/fimmu.2021.766757https://doaj.org/article/cfadb639ae56419a8365902fee7f7c142021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.766757/fullhttps://doaj.org/toc/1664-3224Regulatory T cells (Tregs) are considered important for controlling the onset and development of autoimmune disease. Although studies have shown that miR-21 is expressed at higher levels in Treg cells, it remains largely elusive whether miR-21 regulates the immune-suppressive function of Tregs. In the current study, we generated mice lacking miR-21 specifically in their Tregs and investigated the role of miR-21 in regulating Treg function both in vitro and in vivo. Our study revealed that Tregs lacking miR-21 exhibit normal phenotype and unaltered function in suppressing T cell proliferation and dendritic cell activation in vitro. However, compared with miR-21-sufficient Tregs, they produce significant more IL-17 and IL-10 when under pathogenic Th17-priming condition. Adenoviral delivery of miR-21 into Treg cells is able to reduce the expression of both IL-17 and IL-10. Mechanistic study revealed that miR-21 down-regulates IL-10 expression through direct targeting of IL-10, and suppresses reprogramming of Tregs into IL-17-secreting cells through down-regulating Stat3 activity. However, we detected no significant or marginal difference in the development of various autoimmune diseases between wild type mice and mice with Treg-specific deletion of miR-21. In conclusion, our study demonstrated that miR-21 in Tregs regulates diametrically opposed biological Treg functions and is largely dispensable for the development of autoimmune disease.Jijun SunJijun SunRuiling LiuXiaozhen HeJiang BianWenbo ZhaoWeiyun ShiQingguo RuanFrontiers Media S.A.articlemiR-21immune toleranceimmune-regulationautoimmune diseaseregulatory T cellImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	miR-21 immune tolerance immune-regulation autoimmune disease regulatory T cell Immunologic diseases. Allergy RC581-607
spellingShingle	miR-21 immune tolerance immune-regulation autoimmune disease regulatory T cell Immunologic diseases. Allergy RC581-607 Jijun Sun Jijun Sun Ruiling Liu Xiaozhen He Jiang Bian Wenbo Zhao Weiyun Shi Qingguo Ruan MicroRNA-21 Regulates Diametrically Opposed Biological Functions of Regulatory T Cells
description	Regulatory T cells (Tregs) are considered important for controlling the onset and development of autoimmune disease. Although studies have shown that miR-21 is expressed at higher levels in Treg cells, it remains largely elusive whether miR-21 regulates the immune-suppressive function of Tregs. In the current study, we generated mice lacking miR-21 specifically in their Tregs and investigated the role of miR-21 in regulating Treg function both in vitro and in vivo. Our study revealed that Tregs lacking miR-21 exhibit normal phenotype and unaltered function in suppressing T cell proliferation and dendritic cell activation in vitro. However, compared with miR-21-sufficient Tregs, they produce significant more IL-17 and IL-10 when under pathogenic Th17-priming condition. Adenoviral delivery of miR-21 into Treg cells is able to reduce the expression of both IL-17 and IL-10. Mechanistic study revealed that miR-21 down-regulates IL-10 expression through direct targeting of IL-10, and suppresses reprogramming of Tregs into IL-17-secreting cells through down-regulating Stat3 activity. However, we detected no significant or marginal difference in the development of various autoimmune diseases between wild type mice and mice with Treg-specific deletion of miR-21. In conclusion, our study demonstrated that miR-21 in Tregs regulates diametrically opposed biological Treg functions and is largely dispensable for the development of autoimmune disease.
format	article
author	Jijun Sun Jijun Sun Ruiling Liu Xiaozhen He Jiang Bian Wenbo Zhao Weiyun Shi Qingguo Ruan
author_facet	Jijun Sun Jijun Sun Ruiling Liu Xiaozhen He Jiang Bian Wenbo Zhao Weiyun Shi Qingguo Ruan
author_sort	Jijun Sun
title	MicroRNA-21 Regulates Diametrically Opposed Biological Functions of Regulatory T Cells
title_short	MicroRNA-21 Regulates Diametrically Opposed Biological Functions of Regulatory T Cells
title_full	MicroRNA-21 Regulates Diametrically Opposed Biological Functions of Regulatory T Cells
title_fullStr	MicroRNA-21 Regulates Diametrically Opposed Biological Functions of Regulatory T Cells
title_full_unstemmed	MicroRNA-21 Regulates Diametrically Opposed Biological Functions of Regulatory T Cells
title_sort	microrna-21 regulates diametrically opposed biological functions of regulatory t cells
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/cfadb639ae56419a8365902fee7f7c14
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MicroRNA-21 Regulates Diametrically Opposed Biological Functions of Regulatory T Cells

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