title: Decidual cell regulation of natural killer cell-recruiting chemokines: implications for the pathogenesis and prediction of preeclampsia.
abstract: First trimester human decidua is composed of decidual cells, CD56(bright)CD16(-) decidual natural killer (dNK) cells, and macrophages. Decidual cells incubated with NK cell-derived IFN-γ and either macrophage-derived TNF-α or IL-1β synergistically enhanced mRNA and protein expression of IP-10 and I-TAC. Both chemokines recruit CXCR3-expressing NK cells. This synergy required IFN-γ receptor 1 and 2 mediation via JAK/STAT and NFκB signaling pathways. However, synergy was not observed on neutrophil, monocyte, and NK cell-recruiting chemokines. Immunostaining of first trimester decidua localized IP-10, I-TAC, IFN-γR1, and -R2 to vimentin-positive decidual cells versus cytokeratin-positive interstitial trophoblasts. Flow cytometry identified high CXCR3 levels on dNK cells and minority peripheral CD56(bright)CD16(-) pNK cells and intermediate CXCR3 levels on the majority of CD56(dim)CD16(+) pNK cells. Incubation of pNK cells with either IP-10 or I-TAC elicited concentration-dependent enhanced CXCR3 levels and migration of both pNK cell subsets that peaked at 10 ng/mL, whereas each chemokine at a concentration of 50 ng/mL inhibited CXCR3 expression and pNK cell migration. Deciduae from women with preeclampsia, a leading cause of maternal and fetal morbidity and mortality, displayed significantly lower dNK cell numbers and higher IP-10 and I-TAC levels versus gestational age-matched controls. Significantly elevated IP-10 levels in first trimester sera from women eventually developing preeclampsia compared with controls, identifying IP-10 as a novel, robust early predictor of preeclampsia.
authors: Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, Ohio, USA.
authors: Charles J
authors: CJ
authors: Lockwood
authors: S Joseph
authors: SJ
authors: Huang
authors: Chie-Pein
authors: CP
authors: Chen
authors: Yingqun
authors: Y
authors: Huang
authors: Jie
authors: J
authors: Xu
authors: Saeed
authors: S
authors: Faramarzi
authors: Ozlem
authors: O
authors: Kayisli
authors: Umit
authors: U
authors: Kayisli
authors: Louise
authors: L
authors: Koopman
authors: Dineke
authors: D
authors: Smedts
authors: Lynn F
authors: LF
authors: Buchwalder
authors: Frederick
authors: F
authors: Schatz
mesh_terms: D019002:CD56 Antigen / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D003656:Decidua / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D011225:Pre-Eclampsia / Q000097:blood / Q000209:etiology* / Q000473:pathology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D019707:Receptors, Chemokine / Q000097:blood / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D019002:CD56 Antigen; D018925:Chemokines; D053583:Interleukin-1beta; D007378:Interleukins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019707:Receptors, Chemokine; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
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