Phenotypic and functional features of human Th17 cells.

Phenotypic and functional features of human Th17 cells.
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DOI:
10.1084/jem.20070663
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发表时间:
2007-08-06
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Romagnani S
Romagnani S
中科院分区:
其他
文献类型:
--
作者:
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S

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辅助性T(Th)17细胞代表了一种新的CD 4 + T细胞亚群,其对细胞外微生物具有保护作用,但在小鼠中负责自身免疫性疾病。然而,它们在人类中的特性仅部分已知。我们证明了克罗恩病患者肠道中存在Th 17细胞,其中一些产生白细胞介素(IL)-17和干扰素(IFN)-γ(Th 17/Th 1)。Th 17和Th 17/Th 1克隆均显示IL-23 R、CCR 6和转录因子RORγt的选择性表达,并且它们表现出相似的功能特征,例如帮助B细胞的能力、低细胞毒性和对自体调节性T细胞调节的低敏感性。有趣的是,这些亚群也表达Th 1转录因子T-bet,并且在IL-12存在下刺激这些细胞下调RORγt的表达和IL-17的产生,但诱导IFN-γ。这些作用在IL-23的存在下被部分抑制。在新鲜衍生的产生IL-17的外周血和扁桃体CD 4 + T细胞中观察到类似的受体表达和功能能力。人Th 17细胞选择性标记的展示可能有助于我们了解其致病作用。此外,鉴定共享Th 1和Th 17特征的细胞亚群(其可由IL-12对Th 17细胞的调节引起)可能提出关于Th 17和Th 1之间的发育和/或功能关系的新问题。
T helper (Th) 17 cells represent a novel subset of CD4+ T cells that are protective against extracellular microbes, but are responsible for autoimmune disorders in mice. However, their properties in humans are only partially known. We demonstrate the presence of Th17 cells, some of which produce both interleukin (IL)-17 and interferon (IFN)-γ (Th17/Th1), in the gut of patients with Crohn's disease. Both Th17 and Th17/Th1 clones showed selective expression of IL-23R, CCR6, and the transcription factor RORγt, and they exhibited similar functional features, such as the ability to help B cells, low cytotoxicity, and poor susceptibility to regulation by autologous regulatory T cells. Interestingly, these subsets also expressed the Th1-transcription factor T-bet, and stimulation of these cells in the presence of IL-12 down-regulated the expression of RORγt and the production of IL-17, but induced IFN-γ. These effects were partially inhibited in presence of IL-23. Similar receptor expression and functional capabilities were observed in freshly derived IL-17–producing peripheral blood and tonsillar CD4+ T cells. The demonstration of selective markers for human Th17 cells may help us to understand their pathogenic role. Moreover, the identification of a subset of cells sharing features of both Th1 and Th17, which can arise from the modulation of Th17 cells by IL-12, may raise new issues concerning developmental and/or functional relationships between Th17 and Th1.
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