Immunology for University Students

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 TH17 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 TH17 cells via IFN-γ secreted by the CD56brightCD27+ NK subset. This NK-cell–mediated regulatory response is lost in patients who experience recurrent spontaneous abortions, which results in a prominent TH17 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 TH17-mediated local inflammation.