%0 Journal Article
%T IL-10 signaling in CD4+ T cells is critical for the pathogenesis of collagen-induced arthritis
%A Jian Tao
%A Masahito Kamanaka
%A Jianlei Hao
%A Zhifang Hao
%A Xi Jiang
%A Joe E Craft
%A Richard A Flavell
%A Zhenzhou Wu
%A Zhangyong Hong
%A Liqing Zhao
%A Zhinan Yin
%J Arthritis Research & Therapy
%D 2011
%I BioMed Central
%R 10.1186/ar3545
%X 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).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-¦Ã. 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+¦Ã¦Ä T cells into the arthritic joints.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+¦Ã¦Ä T cells.Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joint capsule and synovial membrane which results in cartilage injury, bone erosion and e
%U http://arthritis-research.com/content/13/6/R212