NDLI: Identification of microRNA-31 as a novel regulator contributing to impaired interleukin-2 production in T cells from patients with systemic lupus erythematosus.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Fan, Wei Liang, Dong Tang, Yuanjia Qu, Bo Cui, Huijuan Luo, Xiaobing Huang, Xinfang Chen, Shunle Higgs, Brandon W. Jallal, Bahija Yao, Yihong Harley, John B. Shen, Nan
Description	Country affiliation: China Author Affiliation: Fan W ( Joint Molecular Rheumatology Laboratory of the Institute of Health Sciences, Shanghai JiaoTong University School of Medicine, Chinese Academy of Sciences, China.)
Abstract	OBJECTIVE: MicroRNAs (miRNAs) function to fine-tune the control of immune cell signaling. It is well established that there are abnormalities in the interleukin-2 (IL-2)-related signaling pathways in systemic lupus erythematosus (SLE). The miR-31 microRNA has been found to be markedly underexpressed in patients with SLE, and thus the present study was undertaken to investigate the role of miR-31 in IL-2 defects in lupus T cells. METHODS: Expression levels of miR-31 were quantitated using TaqMan miRNA assays. Transfection and stimulation of cultured cells followed by TaqMan quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and reporter gene assays were conducted to determine the biologic function of miR-31. NF-AT nuclear translocation and expression were quantitatively measured using an ImageStream cytometer. Bioinformatics analysis, small interfering RNA (siRNA) knockdown, and Western blotting were performed to validate miR-31 targets and effects. RESULTS: The expression of miR-31 was significantly decreased in lupus T cells, and this was positively correlated with the expression of IL-2. Overexpression of miR-31 in T cells increased the production of IL-2 by altering NF-AT nuclear expression and IL2 promoter activity, while knockdown of endogenous miR-31 reduced IL-2 production. RhoA expression was directly repressed by miR-31 in T cells. Of note, siRNA-mediated knockdown of RhoA enhanced IL2 promoter activity and, consequently, up-regulated IL-2 production. RhoA expression was consistently up-regulated and negatively correlated with the levels of miR-31 in lupus T cells. Manipulation of miR-31 expression in lupus T cells restored the expression of IL-2 at both the messenger RNA and protein levels. CONCLUSION: MicroRNA-31 is a novel enhancer of IL-2 production during T cell activation. Dysregulation of miR-31 and its target, RhoA, could be a novel molecular mechanism underlying the IL-2 deficiency in patients with SLE.
File Format	HTM / HTML
ISSN	00043591
e-ISSN	15290131
Journal	Arthritis & Rheumatism
Issue Number	11
Volume Number	64
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2012-11-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Micrornas Promoter Regions, Genetic Research Support, Non-u.s. Gov't Interleukin-2 Signal Transduction Jurkat Cells Rna, Small Interfering Deficiency Gene Expression Regulation Rhoa Gtp-binding Protein Metabolism Nfatc Transcription Factors T-lymphocytes Immunology Lupus Erythematosus, Systemic Genetics Primary Cell Culture Discipline Rheumatic Diseases
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Pharmacology (medical) Rheumatology

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