首页|期刊导航|中华医学杂志（英文版）|Antigen-specific tolerance induced by IL-10 gene modified immature dendritic cells in experimental autoimmune myocarditis in rats
中华医学杂志（英文版）2006，Vol.119Issue(19)：1646-1652,7.
Antigen-specific tolerance induced by IL-10 gene modified immature dendritic cells in experimental autoimmune myocarditis in rats
Antigen-specific tolerance induced by IL-10 gene modified immature dendritic cells in experimental autoimmune myocarditis in rats
摘要
Abstract
Background Experimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder. The initiation and maintenance of autoimmune responses in EAM depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to test the hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells (iDCs) ameliorate EAM and to explore the underlying mechanisms.Methods EAM was induced using the methods of cardiac myosin immunization on day 0 and day 7. Immature and mature bone marrow-derived dendritic cells (BMDCs) were generated without or with the stimulation by lipopolysaccharide (LPS) and the phenotype was analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10 plasmid. 2 × 106/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC,pcDNA3-IL-10 transfected iDC or phosphate buffered saline (PBS) were injected intravenously for treatment 5 days after the first immunization. On day 21, HE staining was performed to detect the myocardial inflammation and T lymphocyte proliferation assay was used to determine the effects of IL-10 gene transfected iDC on autoreactive T cell proliferation. Expression of IκB, the inhibitor of NF-κB pathway, was determined by Western blot. Results BMDCs generated in a medium supplemented with granulocyte-macrophage-colony-stimulating factor (GM-CSF) were relatively immature, as determined by flow cytometry. However, stimulation with LPS induced these cells to become mature (m)DCs with higher levels of surface major histocompatibility complex (MHC)-Ⅱ and costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL-10 transfected iDC,ameliorated the histopathological severity of the myosin induced-EAM, and the effect was lost after the DCs underwent maturation induced by in vitro exposure to LPS. IL-10 gene modified iDC inhibited the antigen specific T cell responses towards cardiac myosin. IκB protein was up-regulated significantly in the IL-10 gene modified iDC group.Conclusions IL-10 gene modified iDC induced antigen-specific tolerance in EAM. The underlying mechanisms may be related to costimulatory molecules down-regulation and NF-κB pathway inhibition.关键词
experimental autoimmune myocarditis/dendritic cell/interleukin-10/nuclear factor-κB/immunotherapyKey words
experimental autoimmune myocarditis/dendritic cell/interleukin-10/nuclear factor-κB/immunotherapy分类
医药卫生引用本文复制引用
LI Wei-min,LI Yue,LIU Wei,GAO Cheng,ZHOU Bao-guo,YANG Shu-sen,WANG Zheng,ZHANG Rui-hong,GAN Run-tao,KONG Yi-hui..Antigen-specific tolerance induced by IL-10 gene modified immature dendritic cells in experimental autoimmune myocarditis in rats[J].中华医学杂志（英文版）,2006,119(19):1646-1652,7.基金项目
This study was supported by Harbin Medical University Postgraduate Creation Foundation (2005). （2005）
