NK cells inhibit T-bet-deficient, autoreactive Th17 cells.

NK cells inhibit T-bet-deficient, autoreactive Th17 cells.
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DOI:
10.1111/j.1365-3083.2012.02773.x
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发表时间:
2012-12
影响因子:
3.7
通讯作者:
Liu R
Liu R
中科院分区:
医学4区
文献类型:
--
作者:
Wu W;Shi S;Ljunggren HG;Cava AL;Van Kaer L;Shi FD;Liu R

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Th 17细胞的分化和维持需要独特的细胞因子环境和谱系特异性转录因子的激活。这个过程似乎是拮抗的转录因子T-bet,它控制的Th 1细胞的分化。考虑到T-bet-缺陷(T-bet-/-)小鼠由于这些细胞的终末成熟缺陷而在很大程度上缺乏自然杀伤(NK)细胞,并且因为NK细胞可以影响T辅助细胞的分化,我们研究了T-bet-缺陷小鼠中NK细胞的缺乏是否有助于增强自身反应性Th 17细胞应答。我们表明,T-bet的缺失使转录因子Rorc和STAT 3对NK细胞提供的刺激的激活具有高度反应性。此外,用野生型NK细胞重建T-bet−/−小鼠通过NK细胞衍生的IFN-γ产生抑制自身反应性Th 17细胞的发育。这些结果确定NK细胞作为自身反应性Th 17细胞和Th 17介导的病理学发展中的关键调节因子。
The differentiation and maintenance of Th17 cells require a unique cytokine milieu and activation of lineage-specific transcription factors. This process appears to be antagonized by the transcription factor T-bet, which controls the differentiation of Th1 cells. Considering that T-bet-deficient (T-bet−/−) mice are largely devoid of natural killer (NK) cells due to a defect in the terminal maturation of these cells, and because NK cells can influence the differentiation of T helper cells, we investigated whether the absence of NK cells in T-bet-deficient mice contributes to the augmentation of autoreactive Th17 cell responses. We show that the loss of T-bet renders the transcription factors Rorc and STAT3 highly responsive to activation by stimuli provided by NK cells. Furthermore, reconstitution of T-bet−/− mice with wild-type NK cells inhibited the development of autoreactive Th17 cells through NK cell-derived production of IFN-γ. These results identify NK cells as critical regulators in the development of autoreactive Th17 cells and Th17-mediated pathology.
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