Differential IL-10 production by DCs determines the distinct adjuvant effects of LPS and PTX in EAE induction
Differential IL-10 production by DCs determines the distinct adjuvant effects of LPS and PTX in EAE induction
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DC 产生的 IL-10 差异决定了 LPS 和 PTX 在 EAE 诱导中的不同佐剂作用
DOI：
10.1002/eji.201343744
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发表时间：
2014
影响因子：
5.4
通讯作者：
Sun Bing
中科院分区：
文献类型：
--
作者：
Zhou Haiyan;Wang Yanming;Lian Qiaoshi;Yang Bo;Ma Yonglei;Wu Xiaodong;Sun Shuhui;Liu Yongjun;Sun Bing
百日咳毒素（PTX）被用作佐剂，以诱导EAE在小鼠作为MS的模型。虽然LPS和PTX是相似的，在他们的能力成熟的树突状细胞（DC）和在他们的佐剂性质，在这里，我们证明，LPS不诱导EAE的发展。我们还证明了用PTX处理的DC（PTX-DC）能够诱导EAE，而用LPS处理的DC（LPS-DC）不能诱导EAE。我们确定LPS-DCs和PTX-DCs之间的关键区别在于LPS-DCs产生更大量的IL-10。在共培养系统中，与用LPS处理的WT DC相比，用LPS处理的IL-10−/−-DC促进更强的IFN-γ和IL-17产生以及T细胞增殖。最后，我们证明，当用LPS处理的IL-10−/−-DC用作佐剂时，可以成功诱导EAE，而使用过表达IL-10的PTX-DC作为佐剂显著控制EAE的发展。这些结果表明，LPS不能诱导EAE是基于在靶向DC中诱导高水平的IL-10，从而提供了对负责诱导EAE的机制的深入了解。
Pertussis toxin (PTX) is used as an adjuvant to induce EAE in mice as a model of MS. Although LPS and PTX are similar in their ability to mature dendritic cells (DCs) and in their adjuvant properties, here we demonstrate that LPS does not induce EAE development. We also demonstrate that DCs treated with PTX (PTX‐DCs) are able to induce EAE, whereas DCs treated with LPS (LPS‐DCs) fail to induce EAE. We determine that a key difference between LPS‐DCs and PTX‐DCs is that LPS‐DCs produce larger amounts of IL‐10. IL‐10−/−‐DCs treated with LPS promote stronger IFN‐γ and IL‐17 production and T‐cell proliferation than WT DCs treated with LPS in a coculture system. Finally, we demonstrate that EAE can be successfully induced when IL‐10−/−‐DCs treated with LPS are used as an adjuvant, whereas the use of PTX‐DCs overexpressing IL‐10 as an adjuvant markedly controls EAE development. These results indicate that the inability of LPS to induce EAE is based on the induction of high levels of IL‐10 in the targeted DCs, providing insight into the mechanisms responsible for the induction of EAE.