title: Decreased microRNA-142-3p/5p expression causes CD4+ T cell activation and B cell hyperstimulation in systemic lupus erythematosus.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Second Xiangya Hospital and Central South University, Changsha, Hunan, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Ding
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Liang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Gongping
authors.initials: G
authors.lastname: Liang
authors.forename: Hai
authors.initials: H
authors.lastname: Long
authors.forename: Sha
authors.initials: S
authors.lastname: Zhao
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Heng
authors.initials: H
authors.lastname: Yin
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D006657:Histones; C555159:MIRN142 microRNA, human; D035683:MicroRNAs