Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells
Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells
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DOI：
10.1038/ni1496
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发表时间：
2007-09-01
影响因子：
30.5
通讯作者：
Sallusto, Federica
中科院分区：
文献类型：
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作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
产生IL-17(IL-17)的CD4(+)辅助T细胞(T-H-17细胞)与宿主防御和自身免疫性疾病有关。在小鼠体内，T-H-17细胞的分化需要转化生长因子-β和IL-6以及转录因子ROR-γt。本文报道了对于人类原始的CD4+T细胞，ROR-γt的表达和T-H-17极化被IL-1β诱导，IL-6增强，但被转化生长因子-β和IL-12抑制。单核细胞和常规树突状细胞(而不是微生物刺激激活的单核细胞来源的树突状细胞)有效地诱导T-H-17启动，这种功能与抗原提呈细胞产生IL-1b和IL-6有关，但与IL-12无关。我们的结果确定了促进人T-H-17细胞极化的细胞因子、抗原提呈细胞和微生物产物，并强调了人和小鼠对T-H-17细胞分化要求的重要差异。
Interleukin 17 (IL-17)-producing CD4(+) helper T cells (T-H-17 cells) have been linked to host defense and autoimmune diseases. In mice, the differentiation of T-H-17 cells requires transforming growth factor-beta and IL-6 and the transcription factor ROR gamma t. We report here that for human naive CD4+ T cells, ROR gamma t expression and T-H-17 polarization were induced by IL-1 beta and enhanced by IL-6 but were suppressed by transforming growth factor-beta and IL-12. Monocytes and conventional dendritic cells, but not monocyte-derived dendritic cells activated by microbial stimuli, efficiently induced T-H-17 priming, and this function correlated with antigen-presenting cell production of IL-1b and IL-6 but not IL-12. Our results identify cytokines, antigen-presenting cells and microbial products that promote the polarization of human T-H-17 cells and emphasize an important difference in the requirements for the differentiation of T-H-17 cells in humans and mice.