Decidual Natural Killer Cells

The most abundant maternal immune cell present in the pregnant uterus is the decidual natural killer (NK) cell. In the non-pregnant uterus, NK cells increase in number in the late secretory phase of the menstrual cycle. They then accumulate in the decidua during early pregnancy and by the end of the first trimester, decidual NK cells make up 70% of the immune cells in the uterine environment. As part of the innate immune system and named for their cytotoxicity, NK cells found in the blood are able to kill invading pathogens and tumour cells. However, decidual NK cells have been demonstrated to differ from blood NK cells in a number of ways, and crucially are not cytotoxic to “non-self” fetal cells. There is evidence that decidual NK cells produce a number of angiogenic factors and cytokines that may aid spiral artery remodelling and development of the placenta, a crucial step in the first trimester of pregnancy.

 

dnk cells

From Remodelling at the maternal-fetal interface: relevance to human pregnancy disorders

 

The importance of dNK cells in spiral artery remodelling was first demonstrated in transgenic mice lacking NK cells. Mice lacking NK cells displayed abnormal spiral arteries and 50% fetal death by day 10 of gestation. Since these experiments in mice, there has been increased interest in studying dNK in the human. Recently, transformation of the spiral arteries in the absence of trophoblast but presence of dNK has been demonstrated, and factors secreted by dNK have been shown to destabilise spiral arteries. Aberrant functioning of dNK cells has also been implicated in pregnancy disorders including recurrent miscarriage, pre-eclampsia and intra-uterine growth restriction. We are interested in the factors produced by dNK and the effect of these factors on the endothelial cells and vascular smooth muscle cells that make up spiral arteries. We are also interested in the factors secreted by NK cells and what receptors they express on their cell surface.

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