Trained Memory of Human Uterine NK Cells Enhances Their Function in Subsequent Pregnancies

Moriya Gamliel, Debra Goldman-Wohl, Batya Isaacson, Chamutal Gur, Natan Stein, Rachel Yamin, Michael Berger, Myriam Grunewald, Eli Keshet, Yoach Rais, Chamutal Bornstein, Eyal David, Adam Jelinski, Iris Eisenberg, Caryn Greenfield, Arbel Ben-David, Tal Imbar, Ronit Gilad, Ronit Haimov-Kochman, David MankutaMatan Elami-Suzin, Ido Amit, Jacob H. Hanna, Simcha Yagel, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

219 Scopus citations

Abstract

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. Natural killer cells are present in the human decidua, regulating trophoblast invasion and angiogenesis. Here, Gamliel et al. report on a special subset of human decidual natural killer cells, which “remember” pregnancy and better support subsequent pregnancies. This might explain why first pregnancies are at increased risk of developing diseases of poor placentation.

Original languageAmerican English
Pages (from-to)951-962.e5
JournalImmunity
Volume48
Issue number5
DOIs
StatePublished - 15 May 2018

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

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

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