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Article
Nature Medicine 12, 1065 - 1074 (2006)
Published online: 6 August 2006 | doi:10.1038/nm1452
Decidual NK cells regulate key developmental processes at the human fetal-maternal interface
Jacob Hanna1, Debra Goldman-Wohl2,8, Yaron Hamani2, Inbal Avraham3, Caryn Greenfield2, Shira Natanson-Yaron2, Diana Prus4, Leonor Cohen-Daniel1, Tal I Arnon1, Irit Manaster1, Roi Gazit1, Vladimir Yutkin5, Daniel Benharroch6, Angel Porgador7, Eli Keshet3, Simcha Yagel2 & Ofer Mandelboim1,8
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.
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