Cutting edge:: Regulatory T cells induce CD4+CD25-Foxp3- T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-β

Cutting edge:: Regulatory T cells induce CD4+CD25-Foxp3- T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-β
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DOI:
10.4049/jimmunol.178.11.6725
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发表时间:
2007-06-01
影响因子:
4.4
通讯作者:
Strober, Warren
Strober, Warren
中科院分区:
医学2区
文献类型:
--
作者:
Xu, LiLi;Kitani, Atsushi;Strober, Warren

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最近的研究表明,TGF-β 与 IL-6 一起诱导产生 IL-17 的 T 细胞 (Th17) T 细胞的分化。因此,我们检查了 CD4(+)CD25(+)Foxp3(+) 调节性 T 细胞(即先前显示可产生 TGF-β 的细胞)是否充当 Th 17 诱导剂。我们发现,纯化的CD25(+) T细胞(或从Foxp3-GFP敲入小鼠获得的分选的GFP(+) T细胞)激活后产生大量可溶性TGF-β,并且当与CD4(+) CD25(+)FoxP3(-) T细胞在IL-6存在下培养时,诱导后者分化为Th17细胞。也许更重要的是,激活后,CD4+ CD25(+)Foxp3(+) (GFP(+)) T 细胞本身在 IL-6 存在(且不存在外源 TGF-β 的情况下)分化为 Th17 细胞。这些结果表明CD4+CD25+Foxp3+调节性T细胞可以作为Th17细胞的诱导剂,并且可以分化为Th17细胞。因此,它们对我们理解调节性 T 细胞功能及其可能的治疗用途具有重要意义。
Recent studies have shown that TGF-beta together with IL-6 induce the differentiation of IL-17-producing T cells (Th17) T cells. We therefore examined whether CD4(+)CD25(+)Foxp3(+) regulatory T cells, i.e., cells previously shown to produce TGF-beta, serve as Th 17 inducers. We found that upon activation purified CD25(+) T cells (or sorted GFP(+) T cells obtained from Foxp3-GFP knockin mice) produce high amounts of soluble TGF-beta and when cultured with CD4(+) CD25(+)FoxP3(-) T cells in the presence of IL-6 induce the latter to differentiate into Th17 cells. Perhaps more importantly, upon activation, CD4+ CD25(+)Foxp3(+) (GFP(+)) T cells themselves differentiate into Th17 cells in the presence of IL-6 (and in the absence of exogenous TGF-beta). These results indicate that CD4+ CD25+Foxp3+ regulatory T cells can function as inducers of Th17 cells and can differentiate into Th17 cells. They thus have important implications to our understanding of regulatory T cell function and their possible therapeutic use.