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IL-10 signaling in CD4+ T cells is critical for the pathogenesis of collagen-induced arthritis.

Abstract：

INTRODUCTION:IL-10 is a very important anti-inflammatory cytokine. However, the role of this cytokine in T cells in the pathogenesis of collagen-induced arthritis is unclear. The purpose of this study was to define the role of IL-10 signaling in T cells in the pathogenesis of collagen-induced arthritis. METHODS:IL-10 receptor dominant-negative transgenic (Tg) and control mice were immunized with bovine type II collagen to induce arthritis. The severity of arthritis was monitored and examined histologically. T-cell activation and cytokine production were analyzed using flow cytometry. T-cell proliferation was examined by [3H]thymidine incorporation. Antigen-specific antibodies in serum were measured by ELISA. Foxp3 expression in CD4+ regulatory T cells (Tregs) was determined by intracellular staining or Foxp3-RFP reporter mice. The suppressive function of Foxp3+ CD4+ Tregs was determined in vitro by performing a T-cell proliferation assay. The level of IL-17 mRNA in joints was measured by real-time PCR. A two-tailed nonparametric paired test (Wilcoxon signed-rank test) was used to calculate the arthritis and histological scores. Student's paired or unpaired t-test was used for all other statistical analyses (InStat version 2.03 software; GraphPad Software, San Diego, CA, USA). RESULTS:Blocking IL-10 signaling in T cells rendered mice, especially female mice, highly susceptible to collagen-induced arthritis. T-cell activation and proliferation were enhanced and produced more IFN-γ. The suppressive function of CD4+ Foxp3+ regulatory T cells was significantly impaired in Tg mice because of the reduced ability of Tregs from Tg mice to maintain their levels of Foxp3. This was further confirmed by transferring Foxp3-RFP cells from Tg or wild-type (Wt) mice into a congenic Wt host. The higher level of IL-17 mRNA was detected in inflammatory joints of Tg mice, probably due to the recruitment of IL-17+ γδ T cells into the arthritic joints. CONCLUSION:IL-10 signaling in T cells is critical for dampening the pathogenesis of collagen-induced arthritis by maintaining the function of Tregs and the recruitment of IL-17+ γδ T cells.

journal_name

Arthritis Res Ther

journal_title

Arthritis research & therapy

authors

Tao J,Kamanaka M,Hao J,Hao Z,Jiang X,Craft JE,Flavell RA,Wu Z,Hong Z,Zhao L,Yin Z

doi

10.1186/ar3545

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

R212

issue

eissn

1478-6354

issn

1478-6362

pii

ar3545

journal_volume

pub_type

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IL-10 signaling in CD4+ T cells is critical for the pathogenesis of collagen-induced arthritis.