Inhibition of Th1 differentiation by IL-6 is mediated by SOCS1
Inhibition of Th1 differentiation by IL-6 is mediated by SOCS1
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DOI：
10.1016/s1074-7613(00)00078-9
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发表时间：
2000-12-01
期刊：
影响因子：
32.4
通讯作者：
Rincón, M
中科院分区：
文献类型：
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作者：
Diehl, S;Anguita, J;Rincón, M
白细胞介素6（IL-6）是由免疫和非免疫细胞产生的细胞因子，具有功能多效性和冗余性。IL-6在几种细胞类型的分化中起重要作用。在这里，我们描述了IL-6的一个新功能：CD 4（+）Th 1细胞分化的负调节。虽然IL-6介导的CD 4（+）Th 2分化由IL-4介导，但IL-6对Th 1分化的抑制不依赖于IL-4。IL-6上调活化的CD 4（+）T细胞中细胞因子信号转导抑制因子1（SOCS 1）的表达，从而干扰干扰素γ（IFN γ）诱导的信号转导和转录激活因子1（STAT 1）磷酸化。通过IL-6抑制IFN γ受体介导的信号，可防止IFN γ在CD 4（+）T细胞活化过程中对IFN I基因表达的自动调节，从而防止Th 1分化。因此，IL-6通过两种独立的分子机制促进CD 4（+）Th 2分化和抑制Th 1分化。
Interleukin 6 (IL-6) is a cytokine produced by immune and nonimmune cells and exhibits functional pleiotropy and redundancy. IL-6 plays an important role in the differentiation of several cell types. Here, we describe a novel function of IL-6: the negative regulation of CD4(+) Th1 cell differentiation. While IL-6-directed CD4(+) Th2 differentiation is mediated by IL-4, inhibition of Th1 differentiation by IL-6 is independent of IL-4. IL-6 upregulates suppressor of cytokine signaling 1 (SOCS1) expression in activated CD4(+) T cells, thereby interfering with signal transducer and activator of transcription 1 (STAT1) phosphorylation induced by interferon gamma (IFN gamma). Inhibition of IFN gamma receptor-mediated signals by IL-6 prevents autoregulation of IFN I gene expression by IFN gamma during CD4(+) T cell activation, thereby preventing Th1 differentiation. Thus, IL-6 promotes CD4(+) Th2 differentiation and inhibits Th1 differentiation by two independent molecular mechanisms.