Cutting edge: Alternative signalin of Th17 cell development by sphingosine 1-phosphate
Cutting edge: Alternative signalin of Th17 cell development by sphingosine 1-phosphate
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DOI：
10.4049/jimmunol.178.9.5425
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发表时间：
2007-05-01
影响因子：
4.4
通讯作者：
Goetzl, Edward J.
中科院分区：
文献类型：
--
作者：
Liao, Jia-Jun;Huang, Mei-Chuan;Goetzl, Edward J.
血液和淋巴中的1-磷酸鞘氨醇(S1P)通过1型S1P受体(SIP1)信号控制T细胞的运输和增殖，但抑制干扰素-γ的产生一直是唯一持续观察到的对T细胞细胞因子的影响。S1P促进由抗原攻击的转基因S1P(1)过表达的CD4T细胞转化为Th17细胞的事实表明，S1P-S1P(1)轴可能促进了野生型小鼠Th17细胞的增殖。在一个由抗CD3+抗CD28抗体以及转化生长因子-β1、IL-1和IL-6混合物刺激的CD4T细胞的Th17细胞发育模型中，S1P增加了它们的数量和IL-17的生成活性，与IL-23相同。IL-23对Th1-7细胞生长的促进作用，S1P可被IL-4加干扰素-γ和IL-27所阻断。S1P受体激动剂和下调调节因子FTY720阻止S1P促进Th17细胞发育，暗示FTY720免疫抑制部分归因于抑制Th17介导的炎症。
Sphingosine 1-phosphate (S1P) in blood and lymph controls T cell traffic and proliferation through type 1 S1P receptor (SIP1) signals, but suppression of IFN-gamma generation has been the only consistently observed effect on T cell cytokines. The fact that S1P enhances the development of Th17 cells from Ag-challenged transgenic S1P(1)-overexpressing CD4 T cells suggested that the S1P-S1P(1) axis may promote the expansion of Th17 cells in wild-type mice. In a model of Th17 cell development from CD4 T cells stimulated by anti-CD3 plus anti-CD28 Abs and a mixture of TGF-beta 1, IL-1, and IL-6, S1P enhanced their number and IL-17-generating activity the same as IL-23. As for IL-23 enhancement of Thl 7 cell development, that by S1P was prevented by IL-4 plus IFN-gamma and by IL-27. The prevention of S1P augmentation of Th17 cell development by the S1P receptor agonist and down-regulator FTY720 implies that FTY720 immunosuppression is attributable partially to inhibition of Th17-mediated inflammation.