title: Decidual NK cells regulate key developmental processes at the human fetal-maternal interface.
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.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hanna
authors.forename: Debra
authors.initials: D
authors.lastname: Goldman-Wohl
authors.forename: Yaron
authors.initials: Y
authors.lastname: Hamani
authors.forename: Inbal
authors.initials: I
authors.lastname: Avraham
authors.forename: Caryn
authors.initials: C
authors.lastname: Greenfield
authors.forename: Shira
authors.initials: S
authors.lastname: Natanson-Yaron
authors.forename: Diana
authors.initials: D
authors.lastname: Prus
authors.forename: Leonor
authors.initials: L
authors.lastname: Cohen-Daniel
authors.forename: Tal I
authors.initials: TI
authors.lastname: Arnon
authors.forename: Irit
authors.initials: I
authors.lastname: Manaster
authors.forename: Roi
authors.initials: R
authors.lastname: Gazit
authors.forename: Vladimir
authors.initials: V
authors.lastname: Yutkin
authors.forename: Daniel
authors.initials: D
authors.lastname: Benharroch
authors.forename: Angel
authors.initials: A
authors.lastname: Porgador
authors.forename: Eli
authors.initials: E
authors.lastname: Keshet
authors.forename: Simcha
authors.initials: S
authors.lastname: Yagel
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D019002:CD56 Antigen / Q000276:immunology; D003656:Decidua / Q000166:cytology*; D005260:Female; D005333:Fetus / Q000166:cytology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000502:physiology*; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D055629:Natural Cytotoxicity Triggering Receptor 2; D055628:Natural Cytotoxicity Triggering Receptor 3; D011247:Pregnancy / Q000276:immunology*; D019707:Receptors, Chemokine / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000502:physiology; D054340:Receptors, KIR; D014327:Trophoblasts / Q000378:metabolism / Q000502:physiology*
chemical_list: D043925:Angiogenesis Inducing Agents; D015703:Antigens, CD; D019002:CD56 Antigen; D016209:Interleukin-8; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008562:Membrane Glycoproteins; C112837:NCR2 protein, human; C431710:NCR3 protein, human; D055629:Natural Cytotoxicity Triggering Receptor 2; D055628:Natural Cytotoxicity Triggering Receptor 3; D019707:Receptors, Chemokine; D011971:Receptors, Immunologic; D054340:Receptors, KIR