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MicroRNA-125b regulates Th17/Treg cell differentiation and is associated with juvenile idiopathic arthritis

查看全文 作　　者：Zhi-Dan [1,2]Fan;Qian [1]Cao;Na [2]Huang;Le [2]Ma;Hui-Hui [2]Ma;Ya-Yuan [2]Zhang;Hai-Guo [2]Yu;Guo-Ping [1]Zhou 高影响力作者 机构地区：[1]Department of Pediatrics,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China;[2]Department of Rheumatology and Immunology,Children's Hospital of Nanjing Medical University,Nanjing 210008,China高影响力机构 出　　处：《World Journal of Pediatrics》索引2020年第16卷第1期,共12页高影响力期刊 基　　金：This study was supported by National Natural Science Foundation of China(Nos.81202345,81771762,81170661 and 31640048);Nanjing Science and Technology Development Program(No.201503003)。 摘　　要：Background Juvenile idiopathic arthritis(JIA)is the most common rheumatic disease in childhood driven by aberrant pathways of T-cell activation.T helper 17(Th17)/regulatory T cell(Treg)imbalance plays critical roles in the pathogenesis of arthritis.MicroRNA-125b(miR-125b)was upregulated after the activation of the initial CD4^+T cells,and could regulate the differentiation of CD4^+T cells.However,the effects of miR-125b on Th17/Treg imbalance and differentiation of Th 17/Treg cells remain unknown.Methods In this study,we evaluated the expression of miR-125b in the peripheral blood mononuclear cells(PBMCs)of children with JIA,and the relationship of miR-125b with Th17/Treg imbalance.Then,we used lentivirus vector-mediated overexpression technology to investigate the regulatory function of miR-125b in CD4^+T cells or dendritic cell/CD4^+T co-culture system.Results Decreased miR-125b expression in PBMCs and CD4^+T cells of JIA patients was negatively correlated with the ratio of Th17/Treg cells.It also correlated negatively with retinoic acid receptor-related orphan receptorγt but positively with Forkhead box protein 3 at transcriptional levels.Furthermore,we found that miR-125b overexpression inhibited Th17 cell differentiation,whereas facilitated the differentiation of Treg cells.MiR-125b upregulation led to the decrease of Th 17-secreting cytokines but the increase of the Treg-secreting cytokines.Conclusions Our results demonstrate that miR-125b participated in regulating Thl7/Treg cell differentiation and imbalance in JIA patients.These findings provide novel insight into the critical role of miR-125b in the Th17/Treg imbalance of JIA,and raise the distinct possibility that miR-125b may prove to be a potential therapeutic target for JIA. 关 键 词：CD4^+T-cell differentiation Juvenile idiopathic arthritis MicroRNA-125b Th17cells Treg cells
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