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Open Access Research article

Interleukin-10 attenuation of collagen-induced arthritis is associated with suppression of interleukin-17 and retinoid-related orphan receptor γt production in macrophages and repression of classically activated macrophages

Liang Ye123, Zhongyang Wen123, Yanqun Li123, Bingni Chen123, Ting Yu123, Lanying Liu13, Jinshun Zhang123, Yanmei Ma123, Shuying Xiao13, Liping Ding123, Li Li123 and Zhong Huang123*

Author Affiliations

1 Institute of Biological Therapy, Shenzhen University School of Medicine, Nanhai Ave 3688, Shenzhen, Guangdong 518060, China

2 Department of Pathogen Biology and Immunology, Shenzhen University School of Medicine, Nanhai Ave 3688, Shenzhen, Guangdong 518060, China

3 Shenzhen City Shenzhen University Immunodiagnostic Technology Platform, Nanhai Ave 3688, Shenzhen, Guangdong 518060, China

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Arthritis Research & Therapy 2014, 16:R96  doi:10.1186/ar4544

Published: 16 April 2014

Abstract

Introduction

Our objective in the present study was to determine the signaling pathway of interleukin 10 (IL-10) for modulating IL-17 expression in macrophages and the importance of this mediation in collagen-induced arthritis (CIA).

Methods

IL-10-knockout (IL-10−/−) mice and wild-type (WT) mice were immunized with chicken type II collagen (CII) to induce arthritis. The expression levels of IL-17 and retinoid-related orphan receptor γt (RORγt) in macrophages and joint tissues of IL-10−/− and WT mice were analyzed by enzyme-linked immunosorbent assay, quantitative RT-PCR (qRT-PCR) and Western blotting. The F4/80 macrophages and positive IL-17-producing macrophages in synovial tissues of the mice were determined by immunohistochemistry. The populations of classically activated macrophage (M1) and alternatively activated macrophage (M2) phenotypes were analyzed by flow cytometry. The expression of genes associated with M1 and M2 markers was analyzed by qRT-PCR.

Results

Compared to WT mice, IL-10−/− mice had exacerbated CIA development, which was associated with increased production of T helper 17 cell (Th17)/Th1 proinflammatory cytokines and CII-specific immunoglobulin G2a antibody after CII immunization. Macrophages in IL-10−/− mice had increased amounts of IL-17 and RORγt compared with the amounts in WT mice with CIA. Immunofluorescence microscopy showed that the number of IL-17-producing macrophages in synovial tissues was significantly higher in IL-10−/− mice than in WT mice. IL-10 deficiency might promote macrophage polarization toward the proinflammatory M1 phenotype, which contributes to the rheumatoid arthritis inflammation response.

Conclusion

IL-10 inhibits IL-17 and RORγt expression in macrophages and suppresses macrophages toward the proinflammatory M1 phenotype, which is important for the role of IL-10 in mediating the pathogenesis of CIA.