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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Gaynor, Louise M 

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.

Description

Keywords

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

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

5

Publisher

Springer Science and Business Media LLC
Sponsorship
British Heart Foundation (None)
Medical Research Council (G0900101)
British Heart Foundation (None)
Wellcome Trust (094073/Z/10/Z)
This work was supported by the Wellcome Trust, the Medical Research Council, the Centre for Trophoblast Research and the British Heart Foundation.