MHC-dependent inhibition of uterine NK cells impedes fetal growth and decidual vascular remodelling

Nat Commun. 2014 Feb 28:5:3359. doi: 10.1038/ncomms4359.

Abstract

NK cells express variable receptors that engage polymorphic MHC class I molecules and regulate their function. Maternal NK cells accumulate at the maternal-fetal interface and can interact with MHC class I molecules from both parents. The relative contribution of the two sets of parental MHC molecules to uterine NK cell function is unknown. Here we show that, in mice, maternal and not paternal MHC educates uterine NK cells to mature and acquire functional competence. The presence of an additional MHC allele that binds more inhibitory than activating NK cell receptors results in suppressed NK cell function, compromised uterine arterial remodelling and reduced fetal growth. Notably, reduced fetal growth occurs irrespectively of the parental origin of the inhibitory MHC. This provides biological evidence for the impact of MHC-dependent NK inhibition as a risk factor for human pregnancy-related complications associated with impaired arterial remodelling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Fetal Development / genetics
  • Fetal Development / physiology*
  • Genes, MHC Class I / genetics
  • Genes, MHC Class I / physiology*
  • H-2 Antigens / genetics
  • H-2 Antigens / physiology
  • Immunohistochemistry
  • Killer Cells, Natural / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Microscopy, Confocal
  • Pregnancy
  • Uterus / cytology*
  • Vascular Remodeling / genetics
  • Vascular Remodeling / physiology*

Substances

  • H-2 Antigens
  • H-2Kb protein, mouse