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

doi:10.1038/nm1452

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 journal › Article › peer-review

1421 Scopus citations

Abstract

Human CD56^bright 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 language	English
Pages (from-to)	1065-1074
Number of pages	10
Journal	Nature Medicine
Volume	12
Issue number	9
DOIs	https://doi.org/10.1038/nm1452
State	Published - 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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Hanna, J., Goldman-Wohl, D., Hamani, Y., Avraham, I., Greenfield, C., Natanson-Yaron, S., Prus, D., Cohen-Daniel, L., Arnon, T. I., Manaster, I., Gazit, R., Yutkin, V., Benharroch, D., Porgador, A., Keshet, E., Yagel, S., & Mandelboim, O. (2006). Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nature Medicine, 12(9), 1065-1074. https://doi.org/10.1038/nm1452

@article{029edbc128214aaf89ed7b6833ca0850,

title = "Decidual NK cells regulate key developmental processes at the human fetal-maternal interface",

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.",

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

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.",

year = "2006",

month = sep,

doi = "10.1038/nm1452",

language = "אנגלית",

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Hanna, J, Goldman-Wohl, D, Hamani, Y, Avraham, I, Greenfield, C, Natanson-Yaron, S, Prus, D, Cohen-Daniel, L, Arnon, TI, Manaster, I, Gazit, R, Yutkin, V, Benharroch, D, Porgador, A, Keshet, E, Yagel, S & Mandelboim, O 2006, 'Decidual NK cells regulate key developmental processes at the human fetal-maternal interface', Nature Medicine, vol. 12, no. 9, pp. 1065-1074. https://doi.org/10.1038/nm1452

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T1 - Decidual NK cells regulate key developmental processes at the human fetal-maternal interface

AU - Hanna, Jacob

AU - Goldman-Wohl, Debra

AU - Hamani, Yaron

AU - Avraham, Inbal

AU - Greenfield, Caryn

AU - Natanson-Yaron, Shira

AU - Prus, Diana

AU - Cohen-Daniel, Leonor

AU - Arnon, Tal I.

AU - Manaster, Irit

AU - Gazit, Roi

AU - Yutkin, Vladimir

AU - Benharroch, Daniel

AU - Porgador, Angel

AU - Keshet, Eli

AU - Yagel, Simcha

AU - Mandelboim, Ofer

N1 - 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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N2 - 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.

AB - 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.

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ER -

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

Abstract

Bibliographical note

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