Decidual NK cells regulate key developmental processes at the human fetal-maternal interface

Jacob Hanna, Debra Goldman-Wohl, Yaron Hamani, Inbal Avraham, Caryn Greenfield, Shira Natanson-Yaron, Diana Prus, Leonor Cohen-Daniel, Tal I. Arnon, Irit Manaster, Roi Gazit, Vladimir Yutkin, Daniel Benharroch, Angel Porgador, Eli Keshet, Simcha Yagel*, Ofer Mandelboim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1374 Scopus citations

Abstract

Human CD56bright NK cells accumulate in the maternal decidua during pregnancy and are found in direct contact with fetal trophoblasts. Several mechanisms have been proposed to explain the inability of NK cells to kill the semiallogeneic fetal cells. However, the actual functions of decidual NK (dNK) cells during pregnancy are mostly unknown. Here we show that dNK cells, but not peripheral blood-derived NK subsets, regulate trophoblast invasion both in vitro and in vivo by production of the interleukin-8 and interferon-inducible protein-10 chemokines. Furthermore, dNK cells are potent secretors of an array of angiogenic factors and induce vascular growth in the decidua. Notably, such functions are regulated by specific interactions between dNK-activating and dNK-inhibitory receptors and their ligands, uniquely expressed at the fetal-maternal interface. The overall results support a 'peaceful' model for reproductive immunology, in which elements of innate immunity have been incorporated in a constructive manner to support reproductive tissue development.

Original languageAmerican English
Pages (from-to)1065-1074
Number of pages10
JournalNature Medicine
Volume12
Issue number9
DOIs
StatePublished - Sep 2006

Bibliographical note

Funding Information:
We would like to thank O. Wald, N. Stern, G. Cohen, G. Katz, T. Gonen-Gross and S. Cohen for assistance. We would like to also thank I. Ariel and A. Peled for discussion. O.M. is supported by research grants from the Israel Cancer Research Foundation, The Israel Science Foundation, European Commission (QLK2-CT-2002-011112) and the Israeli Cancer Research Institute. S.Y. is supported by a grant from the Office of the Chief Scientist, Israel Ministry of Health (5695). J.H. is supported by fellowships from the Foulkes Foundation and Israeli Ministry of Education.

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