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Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):E231-40. doi: 10.1073/pnas.1206322110. Epub 2012 Dec 27.

Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface.

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Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Anhui 230027, China.


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-γ 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.

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