Format

Send to

Choose Destination
World J Pediatr. 2019 May 17. doi: 10.1007/s12519-019-00265-z. [Epub ahead of print]

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

Author information

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.
3
Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. yuhaiguo53@126.com.

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 ╬│t 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.

KEYWORDS:

CD4+ T-cell differentiation; Juvenile idiopathic arthritis; MicroRNA-125b; Th17 cells; Treg cells

PMID:
31102153
DOI:
10.1007/s12519-019-00265-z

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center