title: Decidual NK cells alter in vitro first trimester extravillous cytotrophoblast migration: a role for IFN-gamma.
abstract: Abnormal placentation results in either inadequate (consequences: recurrent miscarriage, intrauterine growth restriction, and preeclampsia) or overzealous (consequences: placenta accreta, increta, and percreta) placentation. NK cells dominate in first trimester decidua and probably control extravillous cytotrophoblast (EVT) invasion. We examined this interaction in a novel way, using NK cells and villous explants from concordant first trimester pregnancies cocultured using a new collagen (two-dimensional) model of placentation. Decidual NK (dNK) cells exerted contact-independent inhibition of normal cytotrophoblast migration, associated with changes in the cytotrophoblast expression of metalloproteases-2 and -9, and plasminogen activator inhibitor-1. dNK cells did not affect EVT proliferation and apoptosis, and cell column formation. dNK cell effects were partially reversed by neutralizing Abs against IFN-gamma. We provide ex vivo human evidence of a direct role for dNK in modulating EVT differentiation as they form columns and then migrate from anchoring villi.
authors.affiliation: Department of Obstetrics and Gynaecology, University of British Columbia, 2H30-4500 Oak Street, Vancouver, BC, Canada.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Hu
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dutz
authors.forename: Colin D
authors.initials: CD
authors.lastname: MacCalman
authors.forename: Paul
authors.initials: P
authors.lastname: Yong
authors.forename: Rusung
authors.initials: R
authors.lastname: Tan
authors.forename: Peter
authors.initials: P
authors.lastname: von Dadelszen
mesh_terms: D000328:Adult; D002450:Cell Communication; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D007694:Killer Cells, Natural / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D010920:Placenta / Q000166:cytology*; D010929:Placentation; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D014327:Trophoblasts / Q000166:cytology*
chemical_list: D007371:Interferon-gamma; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9