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主题:间充质干细胞通过化学因子和一氧化氮共作用介导免疫抑制作用5 u9 h1 t' }7 I+ z
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说明:原文来自Cell Stem Cells,干细胞之家新闻小组成员deron翻译(转帖请注明)
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+ a/ U T1 N9 ?3 e间充质干细胞(MSCs)能够通过未知的机制发挥强大的免疫抑制作用。我们发现MSCs的免疫抑制功能由IFNγ引发,随机伴随着其它三种促炎性因子:TNFα、IL1α或IL1β。这些细胞因子联合激发MSCs高表达几种趋化因子和诱导型NO合酶(iNOS)。趋化因子引导T细胞迁徙至MSCs附近,尔后NO抑制T细胞应答反应。iNOS或IFNγR1缺失的小鼠来源MSCs无此细胞因子诱导的免疫抑制效应。趋化因子受体的阻滞同样消除了免疫抑制作用。应用野生型MSCs(而非iNOS或IFNγR1缺失MSCs),预防了小鼠体内移植物抗宿主疾病的发生,该预防效应在抗IFNγ或iNOS抑制剂存在时失效。野生型MSCs也可以抑制缓发型超敏反应,然而iNOS缺乏的MSCs却可以加重此类反应。因而,促炎性因子通过趋化因子和NO的协同作用,来诱导MSCs的免疫抑制效应。
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原摘要:Mesenchymal stem cells (MSCs) can become potently immunosuppressive through unknown mechanisms. We found that the immunosuppressive function of MSCs is elicited by IFNgamma and the concomitant presence of any of three other proinflammatory cytokines, TNFalpha, IL-1alpha, or IL-1beta. These cytokine combinations provoke the expression of high levels of several chemokines and inducible nitric oxide synthase (iNOS) by MSCs. Chemokines drive T cell migration into proximity with MSCs, where T cell responsiveness is suppressed by nitric oxide (NO). This cytokine-induced immunosuppression was absent in MSCs derived from iNOS(-/-) or IFNgammaR1(-/-) mice. Blockade of chemokine receptors also abolished the immunosuppression. Administration of wild-type MSCs, but not IFNgammaR1(-/-) or iNOS(-/-) MSCs, prevented graft-versus-host disease in mice, an effect reversed by anti-IFNgamma or iNOS inhibitors. Wild-type MSCs also inhibited delayed-type hypersensitivity, while iNOS(-/-) MSCs aggravated it. Therefore, proinflammatory cytokines are required to induce immunosuppression by MSCs through the concerted action of chemokines and NO.
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