title: Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface.
abstract: 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.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences,  University of Science and Technology of China, Anhui 230027,  China.
authors.forename: Binqing
authors.initials: B
authors.lastname: Fu
authors.forename: Xianchang
authors.initials: X
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.forename: Xianhong
authors.initials: X
authors.lastname: Tong
authors.forename: Bin
authors.initials: B
authors.lastname: Ling
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
mesh_terms: D000026:Abortion, Habitual / Q000209:etiology / Q000276:immunology / Q000473:pathology; D000328:Adult; D000818:Animals; D019002:CD56 Antigen / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003656:Decidua / Q000276:immunology / Q000473:pathology; D005260:Female; D005333:Fetus / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism; D007519:Isoantigens / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: D019002:CD56 Antigen; D016207:Cytokines; D007519:Isoantigens; C522918:NCAM1 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma