Immunity
Volume 48, Issue 5, 15 May 2018, Pages 951-962.e5
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Article
Trained Memory of Human Uterine NK Cells Enhances Their Function in Subsequent Pregnancies

https://doi.org/10.1016/j.immuni.2018.03.030Get rights and content
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Highlights

  • A unique subset of human natural killer cells exists in repeated pregnancies

  • These NK cells, termed PTdNKs, express increased amounts of NKG2C and LILRB1

  • PTdNKs secrete increased levels of IFN-γ and VEGFα; the latter supports vascularization

Summary

Natural killer cells (NKs) are abundant in the human decidua, regulating trophoblast invasion and angiogenesis. Several diseases of poor placental development are associated with first pregnancies, so we thus looked to characterize differences in decidual NKs (dNKs) in first versus repeated pregnancies. We discovered a population found in repeated pregnancies, which has a unique transcriptome and epigenetic signature, and is characterized by high expression of the receptors NKG2C and LILRB1. We named these cells Pregnancy Trained decidual NK cells (PTdNKs). PTdNKs have open chromatin around the enhancers of IFNG and VEGFA. Activation of PTdNKs led to increased production and secretion of IFN-γ and VEGFα, with the latter supporting vascular sprouting and tumor growth. The precursors of PTdNKs seem to be found in the endometrium. Because repeated pregnancies are associated with improved placentation, we propose that PTdNKs, which are present primarily in repeated pregnancies, might be involved in proper placentation.

Keywords

trained immunity
natural killer cells
pregnancy
decidua
gravidity
LILRB1
NKG2C
great obstetrical disorders

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