• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Mucosal immunology >Cholera toxin adjuvant promotes a balanced Th1/Th2/Th17 response independently of IL-12 and IL-17 by acting on Gs alpha in CD11b(+) DCs
【24h】

Cholera toxin adjuvant promotes a balanced Th1/Th2/Th17 response independently of IL-12 and IL-17 by acting on Gs alpha in CD11b(+) DCs

机译：霍乱毒素佐剂通过作用于CD11b（+）DC中的Gs alpha来促进独立于IL-12和IL-17的平衡的Th1 / Th2 / Th17反应

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Despite an extensive literature on the mechanism of action of cholera toxin (CT), we still lack critical information about how the toxin acts as an adjuvant and, especially, which dendritic cells (DCs) are the target cells. Although a T helper type 2 (Th2)-skewing effect of CT is most commonly reported, effective priming of Th17 cells as well as suppression of Th1 responses are well documented. However, the ability of CT to block interferon regulatory factor 8 (IRF8) function and interleukin (IL)-12 production in DCs, which blocks CD8 alpha DC and Th1 cell development, is inconsistent with priming of Th1 and CD8 T cells in many other reports. This prompted us to investigate the adjuvant effect of CT in wild-type, IL-12p40-/-, Batf3-/-, and IL-17A-/- mice and in mice that selectively lack the Gs alpha target protein for CT adenosine diphosphate (ADP)-ribosylation in DCs. We found that CT promoted Th1 priming independently of IL-12, and whereas Th2 and also Th17 responses were augmented, the gut IgA responses did not require IL-17A. Adjuvanticity was intact in Batf3-/- mice, lacking CD8 alpha(+) DCs, but completely lost in mice with Gs alpha-deficient CD11c cells. Thus, our data demonstrate that the adjuvant effect requires Gs alpha expression in CD11b(+) DCs, and that priming of mucosal IgA and CD4 T cells appears unbiased and is independent of IL-12 and IL-17A.
机译：尽管有大量关于霍乱毒素（CT）作用机理的文献，但我们仍然缺乏有关该毒素如何起佐剂作用，尤其是哪些树突状细胞（DC）是靶细胞的关键信息。尽管最常见的报道有CT的T型辅助2型（Th2）倾斜效应，但Th17细胞的有效启动以及Th1反应的抑制已得到了很好的证明。然而，CT阻止DC中干扰素调节因子8（IRF8）功能和白介素（IL）-12产生的能力阻止CD8αDC和Th1细胞发育，这与在许多其他情况下引发Th1和CD8 T细胞不一致报告。这促使我们研究CT在野生型，IL-12p40-/-，Batf3-/-和IL-17A-/-小鼠中以及在选择性缺乏CT腺苷二磷酸Gs alpha目标蛋白的小鼠中的佐剂作用DC中的（ADP）-核糖基化。我们发现CT能够独立于IL-12促进Th1引发，而Th2和Th17反应增强，而肠道IgA反应则不需要IL-17A。在没有CD8 alpha（+）DC的Batf3-/-小鼠中，佐剂是完整的，但是在缺少Gs alpha的CD11c细胞的小鼠中完全丧失了佐剂性。因此，我们的数据证明佐剂作用需要CD11b（+）DC中的Gs alpha表达，并且粘膜IgA和CD4 T细胞的引发似乎是公正的，并且独立于IL-12和IL-17A。

著录项

相似文献

  • 外文文献
  • 中文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号