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 interfaceJacob 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, 81
The Lautenberg Center for General and Tumor Immunology, The Hebrew University–Hadassah Medical School, Jerusalem 91120, Israel. 2
Department of Obstetrics and Gynecology, Hadassah University Hospital–Mount Scopus, Jerusalem 91120, Israel. 3
Department of Molecular Biology, Hadassah Medical School, Jerusalem 91120, Israel. 4
Department of Pathology, Hadassah University Hospital, Jerusalem 91120, Israel. 5
Department of Urology, Hadassah University Hospital, Jerusalem 91120, Israel. 6
Department of Pathology, Ben Gurion University, Beer Sheva 92865, Israel. 7
Department of Microbiology and Immunology, Ben Gurion University, Beer Sheva 92865, Israel. 8
These authors contributed equally to this work.
Correspondence should be addressed to Ofer Mandelboim oferman@md2.huji.ac.il or Simcha Yagel syagel@hadassah.org.il 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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