Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface
Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface
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DOI：
10.1073/pnas.1206322110
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发表时间：
2013-01-15
影响因子：
11.1
通讯作者：
Wei, Haiming
中科院分区：
文献类型：
--
作者：
Fu, Binqing;Li, Xianchang;Wei, Haiming
自然杀伤（NK）细胞在母胎界面大量积聚，但它们在成功妊娠中的确切作用仍不清楚。在这里，我们提供的证据表明，在自然同种异体妊娠期间，T(H)17 细胞和局部炎症可能发生在母胎界面。我们发现蜕膜 NK 细胞通过 CD56(bright)CD27(+) NK 亚群分泌的 IFN-γ 抑制炎症 T(H)17 细胞，从而促进免疫耐受和成功妊娠。这种 NK 细胞介导的调节反应在反复自然流产的患者中消失，导致显着的 T(H)17 反应和广泛的局部炎症。这种局部炎症反应进一步影响 NK 细胞的调节功能，最终导致母胎耐受性丧失。因此，我们的数据通过抑制 T(H)17 介导的局部炎症，将 NK 细胞确定为母胎界面的关键调节细胞。
Natural killer (NK) cells accumulate at the maternal-fetal interface in large numbers, but their exact roles in successful pregnancy remain poorly defined. Here, we provide evidence that T(H)17 cells and local inflammation can occur at the maternal-fetal interface during natural allogenic pregnancies. We found that decidual NK cells promote immune tolerance and successful pregnancy by dampening inflammatory T(H)17 cells via IFN-gamma secreted by the CD56(bright)CD27(+) NK subset. This NK-cell-mediated regulatory response is lost in patients who experience recurrent spontaneous abortions, which results in a prominent T(H)17 response and extensive local inflammation. This local inflammatory response further affects the regulatory function of NK cells, leading to the eventual loss of maternal-fetal tolerance. Thus, our data identify NK cells as key regulatory cells at the maternal-fetal interface by suppressing T(H)17-mediated local inflammation.