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Open Access Highly Accessed Research article

Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis

Jingyi Li12, Ying Wan1, Qiuye Guo1, Liyun Zou1, Jinyu Zhang1, Yongfei Fang2, Jingbo Zhang1, Jinjun Zhang1, Xiaolan Fu1, Hongli Liu1, Liwei Lu3 and Yuzhang Wu1*

Author Affiliations

1 Institute of Immunology, PLA, Third Military Medical University, 30# Gaotanyan Street, District Shipingba, Chongqing 400038, PR China

2 Department of Rheumatology, Southwest Hospital, Third Military Medical University, Chongqing, 30# Gaotanyan Street, District Shipingba, Chongqing 400038, PR China

3 Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Pokfulam Road, Hong Kong, PR China

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Arthritis Research & Therapy 2010, 12:R81  doi:10.1186/ar3006

Published: 11 May 2010

Abstract

Introduction

Increasing evidence indicates that microRNAs (miRNAs) play a critical role in the pathogenesis of inflammatory diseases. The aim of the study was to investigate the expression pattern and function of miRNAs in CD4+ T cells from patients with rheumatoid arthritis (RA).

Methods

The expression profile of miRNAs in CD4+ T cells from synovial fluid (SF) and peripheral blood of 33 RA patients was determined by microarray assay and validated by qRT-PCR analysis. The correlation between altered expression of miRNAs and cytokine levels was determined by linear regression analysis. The role of miR-146a overexpression in regulating T cell apoptosis was evaluated by flow cytometry. A genome-wide gene expression analysis was further performed to identify miR-146a-regulated genes in T cells.

Results

miRNA expression profile analysis revealed that miR-146a expression was significantly upregulated while miR-363 and miR-498 were downregulated in CD4+ T cells of RA patients. The level of miR-146a expression was positively correlated with levels of tumor necrosis factor-alpha (TNF-α), and in vitro studies showed TNF-α upregulated miR-146a expression in T cells. Moreover, miR-146a overexpression was found to suppress Jurkat T cell apoptosis. Finally, transcriptome analysis of miR-146a overexpression in T cells identified Fas associated factor 1 (FAF1) as a miR-146a-regulated gene, which was critically involved in modulating T cell apoptosis.

Conclusions

We have detected increased miR-146a in CD4+ T cells of RA patients and its close correlation with TNF-α levels. Our findings that miR-146a overexpression suppresses T cell apoptosis indicate a role of miR-146a in RA pathogenesis and provide potential novel therapeutic targets.