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

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 H17 cells and local inflammation can occur at the maternal–fetal interface during natural allogenic pregnancies...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-01, Vol.110 (3), p.E231-E240
Main Authors: Fu, Binqing, Li, Xianchang, Sun, Rui, Tong, Xianhong, Ling, Bin, Tian, Zhigang, Wei, Haiming
Format: Article
Language:English
Subjects:
Abortion, Habitual - etiology
Abortion, Habitual - immunology
Abortion, Habitual - pathology
Adult
Animals
Biological Sciences
CD56 Antigen - metabolism
Cytokines - biosynthesis
Decidua - immunology
Decidua - pathology
Female
Fetus - immunology
Humans
Immune Tolerance
Interferon-gamma - metabolism
Isoantigens - metabolism
Killer Cells, Natural - immunology
Male
Maternal-Fetal Exchange - immunology
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Inbred DBA
Mice, Transgenic
PNAS Plus
Pregnancy
Pregnancy Trimester, First - immunology
Th17 Cells - immunology
Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism
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Summary: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 H17 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 H17 cells via IFN-γ secreted by the CD56 ᵇʳⁱᵍʰᵗCD27 ⁺ NK subset. This NK-cell–mediated regulatory response is lost in patients who experience recurrent spontaneous abortions, which results in a prominent T H17 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 H17-mediated local inflammation.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1206322110