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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / etiology
  • Abortion, Habitual / immunology
  • Abortion, Habitual / pathology
  • Adult
  • Animals
  • 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
  • Pregnancy
  • Pregnancy Trimester, First / immunology
  • Th17 Cells / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism

Substances

  • CD56 Antigen
  • Cytokines
  • Isoantigens
  • NCAM1 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Interferon-gamma