NF-kappa B-driven miR-34a impairs Treg/Th17 balance via targeting Foxp3

doi:10.1016/j.jaut.2019.04.018

	NF-kappa B-driven miR-34a impairs Treg/Th17 balance via targeting Foxp3
	Xie, Mengxiao 1,2; Wang, Jingzhe 1; Gong, Wen 1; Xu, Huiling 1; Pan, Xiaoyuan 1; Chen, Yunpeng 1; Ru, Songwei 1; Wang, Hui 1; Chen, Xiaodan 1; Zhao, Yi 3; Li, Jing 4; Yin, Qing 5; Xia, Sheng 1; Zhou, Xiaoming 1; Liu, Xia 1; Shao, Qixiang 1
	2019-08-01
发表期刊	JOURNAL OF AUTOIMMUNITY
ISSN	0896-8411
卷号	102 页码:96-113
摘要	The subset of regulatory T (Treg) cells, with its specific transcription Foxp3, is a unique cell type for the maintenance of immune homeostasis by controlling effector T (Teff) cell responses. Although it is common that a defect in Treg cells with Treg/Teff disorder causes autoimmune diseases; however, the precise mechanisms are not thoroughly revealed. Here, we report that miR-34a could attenuate human and murine Foxp3 gene expression via targeting their 3' untranslated regions (3' UTR). The human miR-34a, increased in peripheral blood mononuclear cells (PBMCs) and CD4(+) T cells from rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) patients, displayed a positive correlation with some serum markers of inflammation including rheumatoid factor (RF), anti-streptolysin antibody (ASO), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as Th17 signature gene ROR gamma t, but inversely correlated with the mRNA expression levels of FOXP3. In addition, murine miR-34a levels were downregulated in TGF-beta-induced Treg cells but upregulated in Th17 cells induced in vitro compared to activated CD4(+) T cells. It has also been demonstrated that elevated miR-34a disrupting Treg/Th17 balance in vivo contributed to the progress of pathogenesis of collagen induced arthritis (CIA) mice. Furthermore, IL-6 and TNF-alpha were responsible for the upregulation of miR-34a and downregulation of Foxp3, which was reverted by the addition of NF-kappa B/p65 inhibitor BAY11-7082, thus indicating that NF-kappa B/p65 inhibited Foxp3 expression in an miR-34a-dependent manner. Finally, IL-6 or TNF-alpha-activated p65 could bind to the miR-34a promotor and enhance its activity, resulting in upregulation of its transcription. Taken together, we show that NF-kappa B activated by inflammatory cytokines, such as IL-6 and TNF-alpha, ameliorates Foxp3 levels via regulating miR-34a expression, which provides a new mechanistic and therapeutic insight into the ongoing of autoimmune diseases.
DOI	10.1016/j.jaut.2019.04.018
收录类别	SCI
语种	英语
资助项目	Chinese National Natural Science Foundation[81273202] ; Chinese National Natural Science Foundation[81671541] ; Chinese National Natural Science Foundation[31400773] ; Clinical Medicine Science & Technology Project of Jiangsu province of China[BL2013024] ; Key Research and Development Programs Social Development Project of Science and Technology Commission Foundation of Jiangsu Province[BE2016721] ; Science and Technology Support Program (Social Development) of Zhenjiang[SH2015055]
WOS研究方向	Immunology
WOS类目	Immunology
WOS记录号	WOS:000479024700008
出版者	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
引用统计	被引频次：59[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/4429
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Liu, Xia; Shao, Qixiang
作者单位	1.Jiangsu Univ, Jiangsu Key Lab Med Sci & Lab Med, Sch Med, Dept Immunol,Reprod Sci Inst, Zhenjiang 212013, Jiangsu, Peoples R China 2.Nanjing Med Univ, Dept Immunol, Nanjing 211166, Jiangsu, Peoples R China 3.Chinese Acad Sci, Inst Comp Technol, Bioinforrnat Res Grp, Key Lab Intelligent Informat Proc, Beijing 100080, Peoples R China 4.Jiangsu Univ, Affiliated Hosp, Dept Rheumatol, Zhenjiang 212001, Jiangsu, Peoples R China 5.Jiangsu Univ, Affiliated Hosp, Dept Clin Lab, Zhenjiang 212001, Jiangsu, Peoples R China
推荐引用方式 GB/T 7714	Xie, Mengxiao,Wang, Jingzhe,Gong, Wen,et al. NF-kappa B-driven miR-34a impairs Treg/Th17 balance via targeting Foxp3[J]. JOURNAL OF AUTOIMMUNITY,2019,102:96-113.
APA	Xie, Mengxiao.,Wang, Jingzhe.,Gong, Wen.,Xu, Huiling.,Pan, Xiaoyuan.,...&Shao, Qixiang.(2019).NF-kappa B-driven miR-34a impairs Treg/Th17 balance via targeting Foxp3.JOURNAL OF AUTOIMMUNITY,102,96-113.
MLA	Xie, Mengxiao,et al."NF-kappa B-driven miR-34a impairs Treg/Th17 balance via targeting Foxp3".JOURNAL OF AUTOIMMUNITY 102(2019):96-113.