• Shu Ding, Yunsheng Liang, Ming Zhao, Gongping Liang, Hai Long, Sha Zhao, Yu Wang, Heng Yin, Peng Zhang, Qing Zhang, and Qianjin Lu.
• Second Xiangya Hospital and Central South University, Changsha, Hunan, China.
• Arthritis Rheum. 2012 Sep 1; 64 (9): 2953-63.

ObjectiveTo examine the role of microRNA-142-3p/5p (miR-142-3p/5p) in the development of autoimmunity in patients with systemic lupus erythematosus (SLE).MethodsMicroRNA-142-3p/5p expression levels were determined by real-time quantitative polymerase chain reaction, and potential target genes were verified using luciferase reporter gene assays. The effects of miR-142-3p/5p on T cell function were assessed by transfection with miR-142-3p/5p inhibitors or mimics. Histone modifications and methylation levels within a putative regulatory region of the miR-142 locus were detected by chromatin immunoprecipitation assay and bisulfite sequencing, respectively.ResultsWe confirmed that miR-142-3p and miR-142-5p were significantly down-regulated in SLE CD4+ T cells compared with healthy controls and observed that miR-142-3p/5p levels were inversely correlated with the putative SLE-related targets signaling lymphocytic activation molecule-associated protein (SAP), CD84, and interleukin-10 (IL-10). We demonstrated that miR-142-3p and miR-142-5p directly inhibit SAP, CD84, and IL-10 translation, and that reduced miR-142-3p/5p expression in CD4+ T cells can significantly increase protein levels of these target genes. Furthermore, inhibiting miR-142-3p/5p in healthy donor CD4+ T cells caused T cell overactivation and B cell hyperstimulation, whereas overexpression of miR-142-3p/5p in SLE CD4+ T cells had the opposite effect. We also observed that the decrease in miR-142 expression in SLE CD4+ T cells correlated with changes to histone modifications and DNA methylation levels upstream of the miR-142 precursor sequence.ConclusionThe results of this study indicate that reduced expression of miR-142-3p/5p in the CD4+ T cells of patients with SLE causes T cell activity and B cell hyperstimulation.Copyright © 2012 by the American College of Rheumatology.

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