Decidual NK cells regulate key developmental processes at the human fetal-maternal interface.
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.
Hanna
Jacob
J
The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Goldman-Wohl
Debra
D
Hamani
Yaron
Y
Avraham
Inbal
I
Greenfield
Caryn
C
Natanson-Yaron
Shira
S
Prus
Diana
D
Cohen-Daniel
Leonor
L
Arnon
Tal I
TI
Manaster
Irit
I
Gazit
Roi
R
Yutkin
Vladimir
V
Benharroch
Daniel
D
Porgador
Angel
A
Keshet
Eli
E
Yagel
Simcha
S
Mandelboim
Ofer
O
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*
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