Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells.

Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells.
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DOI:
10.1002/eji.200838331
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发表时间:
2008-07
影响因子:
5.4
通讯作者:
Xiong, Huabao
Xiong, Huabao
中科院分区:
医学3区
文献类型:
--
作者:
Gu, Yongpeng;Yang, Jianfei;Ouyang, Xinshou;Liu, Weicheng;Li, Hongxing;Yang, Jianjun;Bromberg, Jonathan;Chen, Shu-Hsia;Mayer, Lloyd;Unkeless, Jay C.;Xiong, Huabao

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IL-17和IL-22是由Th 17 T细胞亚群产生的典型细胞因子,但尚不清楚Th 17细胞因子是否可以由其他细胞类型产生。我们证明,IL-10缺陷和IL-10 R缺陷的巨噬细胞与LPS刺激产生高水平的IL-17和IL-22。向IL-10缺陷的巨噬细胞中添加外源性IL-10消除了IL-17的产生。当在Th 17极化条件下培养IL-10缺陷型和IL-10 R缺陷型脾细胞时,产生IL-17的细胞的群体增加,并且培养物产生显著更高水平的IL-17和IL-22。向IL-10缺陷的脾细胞中添加重组IL-10显著降低了产生IL-17的CD 4 + T细胞的百分比。最后,Th 17转录因子RORγt的mRNA在IL-10缺陷的脾细胞和巨噬细胞中显著升高。这些数据表明,Th 17细胞因子和RORγt也在巨噬细胞中表达,并且IL-10通过巨噬细胞和T细胞负调节Th 17细胞因子和RORγt的表达。
IL-17 and IL-22 are typical cytokines produced by the Th17 T cell subset, but it is unclear if Th17 cytokines can be produced by other cell types. We demonstrate that IL-10-deficient and IL-10R-deficient macrophages stimulated with LPS produce high levels of IL-17 and IL-22. Addition of exogenous IL-10 to IL-10-deficient macrophages abolished IL-17 production. When IL-10-deficient and IL-10R-deficient splenocytes were cultured under Th17 polarizing conditions the population of IL-17 producing cells was increased and the cultures produced significantly higher levels of IL-17 and IL-22. The addition of recombinant IL-10 to IL-10-deficient splenocytes significantly decreased the percentage of IL-17-producing CD4+ T cells. Finally, the mRNA for the Th17 transcription factor RORγt was significantly elevated in IL-10-deficient spleen cells and macrophages. These data demonstrate that Th17 cytokines and RORγt are also expressed in macrophages and that IL-10 negatively regulates the expression of Th17 cytokines and RORγt by both macrophages and T cells.
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