Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells
Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells
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DOI：
10.1038/ni1540
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发表时间：
2007-12-01
影响因子：
30.5
通讯作者：
Rostami, Abdolmohamad
中科院分区：
文献类型：
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作者：
Fitzgerald, Denise C.;Zhang, Guang-Xian;Rostami, Abdolmohamad
在缺乏白细胞介素27（IL-27）受体α亚单位的小鼠中，在感染和自身免疫期间发生过度炎症。这种炎症增加的分子机制还不完全清楚。在这里，我们报告说，IL-27上调IL-10的效应T细胞，产生干扰素-γ和表达转录因子T-bet，但不表达转录因子Foxp 3。这些IFN-γ（+）T-bet（+）Foxp 3（-）细胞类似于效应T细胞，其已被鉴定为炎症期间宿主保护性IL- 10的主要来源。IL-27诱导的IL- 10的产生与IL- 17的分泌减少相关，外源性IL- 27通过依赖于IL-10的机制降低过继转移的实验性自身免疫性脑脊髓炎的严重程度。我们的数据表明，IL-27诱导的效应T细胞产生IL- 10有助于IL-27的免疫调节功能。
Excessive inflammation occurs during infection and autoimmunity in mice lacking the alpha- subunit of the interleukin 27 (IL-27) receptor. The molecular mechanisms underlying this increased inflammation are incompletely understood. Here we report that IL-27 upregulated IL-10 in effector T cells that produced interferon-gamma and expressed the transcription factor T- bet but did not express the transcription factor Foxp3. These IFN-gamma(+) T- bet(+) Foxp3(-) cells resembled effector T cells that have been identified as the main source of host-protective IL- 10 during inflammation. IL-27-induced production of IL- 10 was associated with less secretion of IL- 17, and exogenous IL- 27 reduced the severity of adoptively transferred experimental autoimmune encephalomyelitis by a mechanism dependent on IL-10. Our data show that IL-27-induced production of IL- 10 by effector T cells contributes to the immunomodulatory function of IL-27.