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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >IL-10 gene modified dendritic cells induced antigen-specific tolerance in experimental autoimmune myocarditis.
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IL-10 gene modified dendritic cells induced antigen-specific tolerance in experimental autoimmune myocarditis.

机译：IL-10基因修饰的树突状细胞在实验性自身免疫性心肌炎中诱导抗原特异性耐受。

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Experimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder, and the involvement of Th1/Th2 unbalance has been demonstrated. The induction of antigen-specific tolerance is critical for the treatment of EAM and maintenance of immune tolerance. 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 explore the effects of IL-10 gene modified bone-marrow-derived immature dendritic cells (iDCs) on the in vitro and in vivo immune response to cardiac myosin in EAM. EAM was induced using the classic methods of cardiac myosin immunization on day 0 and day 7. 2 x 10(6)/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously for treatment 5 days after the first immunization. On day 21, transthoracic echocardiogram and HE staining wereperformed to detect the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen-specific tolerance induced by IL-10 gene modified iDCs. IL-10 gene modified iDC-treated EAM rats showed improved cardiac function and reduced infiltration of inflammatory cell into myocardium. Serum cytokines data indicated lower Th1 while higher Th2-type responses were induced in the pcDNA3-IL-10-iDC-treated group, suggesting a Th2 polarization. Moreover, IL-10 gene modified iDCs down-regulated MHC-II and costimulatory molecules on the surface of splenocytes and inhibited the antigen-specific immunological responses towards cardiac myosin. Adoptive transfer of IL-10 producing DCs prevented EAM induction. IL-10 gene modified iDCs ameliorates EAM histopathologically and functionally. The underlying mechanisms maybe related to the IL-10 induced Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecules expression.
机译：大鼠实验性自身免疫性心肌炎（EAM）是T细胞介导的疾病，并且已证明Th1 / Th2不平衡的参与。抗原特异性耐受性的诱导对于EAM的治疗和维持免疫耐受性至关重要。 IL-10是一种多营养型免疫调节细胞因子，在不同水平的免疫应答中起作用，因此它已成为治疗自身免疫/炎性疾病的有希望的治疗因子。这项研究旨在探讨IL-10基因修饰的骨髓未成熟树突状细胞（iDC）对EAM中对心肌肌球蛋白的体外和体内免疫应答的影响。在第0天和第7天使用经典的心肌肌球蛋白免疫方法诱导EAM。2x 10（6）/每只大鼠成熟DC（mDC），未成熟DC（iDC），pcDNA3转染的iDC，pcDNA3-IL-10转染的iDC第一次免疫5天后，静脉注射PBS或PBS进行治疗。在第21天，进行经胸超声心动图和HE染色以检测心功能和心肌炎症。 ELISA法检测Th1 / Th2细胞因子，MHC-II分子，流式细胞仪鉴定共刺激分子。进行体外T淋巴细胞增殖测定和DC的过继转移，以确定由IL-10基因修饰的iDC诱导的抗原特异性耐受性。 IL-10基因修饰的iDC处理的EAM大鼠表现出改善的心脏功能，并减少了炎性细胞向心肌的浸润。血清细胞因子数据表明在pcDNA3-IL-10-iDC处理组中，Th1较低，而Th2型应答较高，表明Th2极化。此外，IL-10基因修饰的iDCs下调了脾细胞表面的MHC-II和共刺激分子，并抑制了针对心肌肌球蛋白的抗原特异性免疫反应。产生IL-10的DC的过继转移阻止了EAM的诱导。 IL-10基因修饰的iDC从组织病理学和功能上改善EAM。潜在的机制可能与IL-10诱导的Th2极化和MHC-II分子的下调以及共刺激分子的表达有关。

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