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Published in: World Journal of Pediatrics 1/2020

01-02-2020 | Juvenile Rheumatoid Arthritis | Original Article

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

Authors: Zhi-Dan Fan, Qian Cao, Na Huang, Le Ma, Hui-Hui Ma, Ya-Yuan Zhang, Hai-Guo Yu, Guo-Ping Zhou

Published in: World Journal of Pediatrics | Issue 1/2020

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Abstract

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 Th17/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 receptor γt 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 Th17-secreting cytokines but the increase of the Treg-secreting cytokines.

Conclusions

Our results demonstrate that miR-125b participated in regulating Th17/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.
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Metadata
Title
MicroRNA-125b regulates Th17/Treg cell differentiation and is associated with juvenile idiopathic arthritis
Authors
Zhi-Dan Fan
Qian Cao
Na Huang
Le Ma
Hui-Hui Ma
Ya-Yuan Zhang
Hai-Guo Yu
Guo-Ping Zhou
Publication date
01-02-2020
Publisher
Springer Singapore
Published in
World Journal of Pediatrics / Issue 1/2020
Print ISSN: 1708-8569
Electronic ISSN: 1867-0687
DOI
https://doi.org/10.1007/s12519-019-00265-z

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