Decreased MicroRNA-142-3p/5p Expression Causes CD4+T Cell Activation and B Cell Hyperstimulation in Systemic Lupus Erythematosus

作者：Ding, Shu; Liang, Yunsheng; Zhao, Ming; Liang, Gongping; Long, Hai; Zhao, Sha; Wang, Yu; Yin, Heng; Zhang, Peng; Zhang, Qing; Lu, Qianjin^*

来源：Arthritis and Rheumatism, 2012, 64(9): 2953-2963.

DOI：10.1002/art.34505

• MULTIPLE-SCLEROSIS PATIENTS
• ALTERED EXPRESSION
• DISEASE-ACTIVITY
• SAP
• MICRORNAS
• SLAM
• AUTOIMMUNITY
• CONTRIBUTES
• RESPONSES
• DIFFERENTIATION

Objective. To examine the role of microRNA-142-3p/5p (miR-142-3p/5p) in the development of autoimmunity in patients with systemic lupus erythematosus (SLE). @@@ Methods. MicroRNA-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. \ Results. We 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. @@@ Conclusion. The 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.

• 出版日期2012-9
• 单位中南大学