TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells
TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells
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DOI：
10.1016/j.immuni.2006.01.001
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发表时间：
2006-02-01
期刊：
影响因子：
32.4
通讯作者：
Stockinger, B
中科院分区：
文献类型：
--
作者：
Veldhoen, M;Hocking, RJ;Stockinger, B
我们描述了从初始CD4 T细胞从头产生产生白介素 - 17的T细胞，这是在存在Toll样受体3、Toll样受体4或Toll样受体9刺激的情况下，通过初始CD4 T细胞和天然存在的CD4(+)CD25(+) T细胞（调节性T细胞，Treg）共培养诱导产生的。调节性T细胞可被转化生长因子β1替代，转化生长因子β1与促炎细胞因子白介素 - 6一起，支持产生白介素 - 17的T细胞的分化，这一过程被白介素 - 1β和肿瘤坏死因子α放大。我们未能检测到白介素 - 23在产生白介素 - 17的T细胞分化中的作用，但证实了它对这些细胞的存活和扩增的重要性。转录因子GATA - 3和T - bet以及其靶标Hlx在产生白介素 - 17的T细胞中不存在，并且这些细胞不表达转化生长因子β信号的负调节因子Smad7。我们的数据表明，在存在白介素 - 6的情况下，转化生长因子β1使Th1和Th2分化发生转变，从而产生产生白介素 - 17的T细胞。
We describe de novo generation of IL-17-producing T cells from naive CD4 T cells, induced in cocultures of naive CD4 T cells and naturally occurring CD4(+) CD25(+) T cells (Treg) in the presence of TLR3, TLR4, or TLR9 stimuli. Treg can be substituted by TGF beta 1, which, together with the proinflammatory cytokine IL-6, supports the differentiation of IL-17-producing T cells, a process that is amplified by IL-1 beta and TNF alpha. We could not detect a role for IL-23 in the differentiation of IL-17-producing T cells but confirmed its importance for their survival and expansion. Transcription factors GATA-3 and T-bet, as well as its target Hlx, are absent in IL-17-producing T cells, and they do not express the negative regulator for TGF beta signaling, Smad7. Our data indicate that, in the presence of IL-6, TGF beta 1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells.