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decidual nk cells

Ricardo C Cavalli, Ana Sofia Cerdeira, Elizabeth Pernicone, Henri A Korkes, Suzanne D Burke, Augustine Rajakumar, Ravi I Thadhani, Drucilla J Roberts, Manoj Bhasin, S Ananth Karumanchi, Hernan D Kopcow
Decidual NK (dNK) cells, a distinct type of NK cell, are thought to regulate uterine spiral artery remodeling, a process that allows for increased blood delivery to the fetal-placental unit. Impairment of uterine spiral artery remodeling is associated with decreased placental perfusion, increased uterine artery resistance, and obstetric complications such as preeclampsia and intrauterine growth restriction. Ex vivo manipulation of human peripheral blood NK (pNK) cells by a combination of hypoxia, TGFß-1 and 5-aza-2'-deoxycytidine yields cells with phenotypic and in vitro functional similarities to dNK cells, called idNK cells...
2016: PloS One
L Li, J Tu, Y Jiang, J Zhou, D J Schust
Pregnancy loss is the commonest complication of pregnancy. The causes of pregnancy loss are poorly understood. It has been reported that stimulation of invariant natural killer T (iNKT) cells using α-galactosylceramide (αGC) induces pregnancy loss in mice. Here we investigated the mechanisms, especially the role of regulatory T (Treg) cells, in iNKT cell-mediated pregnancy loss. We found that injection of αGC rapidly induced fetal resorption, activated decidual iNKT cells, decreased the percentage of decidual Treg cells and their interleukin (IL)-10 and transforming growth factor (TGF)-β production, and upregulated the levels of interferon (IFN)-γ, tumor necrosis factor-α, IL-4, and IL-10 in serum...
October 5, 2016: Mucosal Immunology
Judith E Cartwright, Laura James-Allan, Rebecca J Buckley, Alison E Wallace
The pathologies of the dangerous pregnancy complications pre-eclampsia (PE) and fetal growth restriction (FGR) are established in the first trimester of human pregnancy yet we know little of how this happens. Finely tuned interactions between maternal and placental cells are essential for pregnancy to progress without complications; however, the precise nature of this cross-talk and how it can go wrong are crucial questions that remain to be answered. This review summarises recent studies examining the role played by natural killer cells in regulating normal placentation and remodelling...
September 18, 2016: Journal of Reproductive Immunology
Ângela C Crespo, Anita van der Zwan, João Ramalho-Santos, Jack L Strominger, Tamara Tilburgs
To establish a healthy pregnancy the maternal immune system must tolerate fetal allo-antigens, yet remain competent to respond to infections. The ability of decidual NK cells (dNK) to promote migration of fetal extravillous trophoblasts (EVT) and placental growth as well as the capacity of EVT to promote immune tolerance are topics of high interest and extensive research. However, the problem of how dNK and decidual CD8+ T cells (CD8+ dT) provide immunity to infections of the placenta and the mechanisms that regulate their cytolytic function has thus far largely been ignored...
August 2, 2016: Journal of Reproductive Immunology
Shigeru Saito, Yasushi Nakabayashi, Akitoshi Nakashima, Tomoko Shima, Osamu Yoshino
The fetus is a semi-allograft for the maternal host in natural pregnancy, but the fetus is a complete allograft after oocyte donation (OD), and there is greater antigenic dissimilarity with the mother. Thus, OD pregnancy is a good model for understanding how the fetus is protected by the maternal immune system. Recent clinical data have revealed a higher risk of miscarriage, gestational hypertension, preterm birth, and low birth weight with OD pregnancy. There is also a higher incidence of chorionic deciduitis, dense fibrinoid deposits in the chorionic basal plate, inflammatory lesions in the chorionic plate, and C4d deposition on syncytiotrophoblasts in OD pregnancy...
June 20, 2016: Seminars in Immunopathology
Gudrun Meinhardt, Leila Saleh, Gerlinde R Otti, Sandra Haider, Philipp Velicky, Christian Fiala, Jürgen Pollheimer, Martin Knöfler
The maternal uterine environment is likely critical for human placental morphogenesis and development of its different trophoblast subtypes. However, factors controlling growth and differentiation of these cells during early gestation remain poorly elucidated. Herein, we provide evidence that the ligand Wnt5a could be a critical regulator of trophoblast proliferation and survival. Immunofluorescence of tissues and western blot analyses of primary cultures revealed abundant Wnt5a expression and secretion from first trimester decidual and villous stromal cells...
2016: Scientific Reports
H Quillay, H El Costa, M Duriez, R Marlin, C Cannou, Y Madec, C de Truchis, M Rahmati, F Barré-Sinoussi, M T Nugeyre, E Menu
BACKGROUND: During the first trimester of pregnancy, HIV-1 in utero transmission is rare despite the permissivity of the placenta and the decidua (the uterine mucosa during pregnancy) to infection. In the decidua from the first trimester of pregnancy, macrophages (dMs) are the HIV-1 main target cells. Decidual natural killer (dNK) cells account for 70 % of decidual leukocytes. They display distinct phenotype and functions compared to peripheral NK cells. At the periphery, NK cells are involved in the control of HIV-1 infection...
2016: Retrovirology
Tamara Gulic, Gordana Laskarin, Marin Dominovic, Lana Glavan Gacanin, Emina Babarovic, Herman Haller, Daniel Rukavina
PROBLEM: The role of HSP70 and both its constitutive (Hsc) and inducible (Hsp) forms in the pathogenesis of threatened spontaneous abortions was investigated. METHOD OF STUDY: Immunohistology and/or immunofluorescence was used to analyze paraffin-embedded tissue sections, and reverse transcriptase-quantitative polymerase chain reaction and flow cytometry were used for analyses of decidual mononuclear cells (DMCs) and confocal microscopy for the detection of perforin, granulysin, and lysosome-associated membrane protein-1 (LAMP-1) in decidual lymphocytes (DLs)...
August 2016: American Journal of Reproductive Immunology: AJRI
Jenny L Sones, Jeeyeon Cha, Ashley K Woods, Amanda Bartos, Christa Y Heyward, Heinrich E Lob, Catherine E Isroff, Scott D Butler, Stephanie E Shapiro, Sudhansu K Dey, Robin L Davisson
Preeclampsia (PE) is a disorder of pregnancy that manifests as late gestational maternal hypertension and proteinuria and can be life-threatening to both the mother and baby. It is believed that abnormal placentation is responsible for the cascade of events leading to the maternal syndrome. Embryo implantation is critical to establishing a healthy pregnancy. Defective implantation can cause adverse "ripple effects," leading to abnormal decidualization and placentation, retarded fetal development, and poor pregnancy outcomes, such as PE and fetal growth restriction...
March 17, 2016: JCI Insight
Terhi T Piltonen
Women with polycystic ovarian syndrome (PCOS) present with several endometrial abnormalities possibly explaining some of the adverse endometrium-related outcomes in these women. PCOS and an increased miscarriage rate have been suggested to coincide, but the results are conflicting. Recent studies have also shown increased risks of pregnancy-induced hypertension, preeclampsia, and premature delivery that may be related to altered decidualization/placentation in affected women. In the long run, PCOS per se is associated with the occurrence of endometrial cancer (EC), with obesity aggravating the risk...
April 1, 2016: Best Practice & Research. Clinical Obstetrics & Gynaecology
Hasan Namdar Ahmadabad, Sabah Kayvan Jafari, Maryam Nezafat Firizi, Ali Reza Abbaspour, Fahime Ghafoori Gharib, Yusef Ghobadi, Samira Gholizadeh
OBJECTIVE: In the present study, we aimed to evaluate the effects of high doses of dexamethasone (DEX) in early pregnancy on pregnancy outcomes. METHODS: Pregnant BALB/c mice were treated with high-dose DEX in the experimental group or saline in the control group on gestational days (GDs) 0.5 to 4.5. Pregnant mice were sacrificed on GDs 7.5, 13.5, or 18.5 and their peripheral blood, placentas, fetuses, and uterine tissue were collected. Decidual and placenta cell supernatants were examined to evaluate the effect of DEX on the proliferation of mononuclear cells, the quantity of uterine macrophages and uterine natural killer (uNK) cells, and levels of progesterone and 17β-estradiol, as determined by an 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively...
March 2016: Clinical and Experimental Reproductive Medicine
Xuefeng Qi, Mingzhu Lei, Lijuan Qin, Mengjie Xie, Dandan Zhao, Jingyu Wang
Uterine natural killer (uNK) cells are the most abundant lymphocyte population in the feto-maternal interface during early gestation, and uNK cells play a significant role in the establishment and maintenance of pregnancy-related vascularization, as well as in tolerance to the fetus. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible molecule (Fn14), are involved in preventing local cytotoxicity and counterbalancing the cytotoxic function of uNK cells...
May 2016: Immunology
Yael Ophir, Alexandra Duev-Cohen, Rachel Yamin, Pini Tsukerman, Yoav Bauman, Moriya Gamliel, Ofer Mandelboim
Natural Killer (NK) cells are innate immune lymphocytes specializing in recognition and killing of tumors and pathogens, using an array of activating and inhibitory receptors. NK inhibition is mediated by a large repertoire of inhibitory receptors, whereas a limited number of activating NK cell receptors execute NK cell activation. The ligands recognized by the activating receptors are stress-induced, pathogen derived, tumor specific and even self ligands. However, the full spectrum of NK cell receptors and ligands that control NK cell activity remains uncharacterized...
March 27, 2016: Oncotarget
Allison M Felker, B Anne Croy
The decidua basalis of developing mouse implantation sites is highly enriched in CD45(+) leukocytes. In intact, syngeneically mated C57BL/6 decidua basalis examined at gestation day 8.5 by whole-mount in situ immunohistochemistry, leukocyte, but not trophoblast, conjugations were reported. Nothing is known regarding time course, frequency, composition, or importance of physiologic decidual CD45(+) cell pairing. In this study, we confirmed the presence of anti-CD54(+)/anti-CD11a(+) immune synapses in CD45(+) decidual cell conjugates and characterized their cellular heterogeneity...
March 21, 2016: Journal of Leukocyte Biology
Dandan Li, Jian Li
BACKGROUND: The specific causes of recurrent spontaneous abortion (RSA) remain unknown in 37-79% of affected women. The aim of this study was to explore the expression levels of 6 miRNAs in natural killer (NK) cells from the decidua of patients with unexplained RSA (URSA) and to predict the target genes of 3 miRNAs. MATERIAL/METHODS: Two groups were examined: URSA (n=20) and controls (n=20). Flow cytometry analysis was used to identify NK cells isolated from the decidua...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Lucy Leon, Allison M Felker, Vanessa R Kay, Megan M Tu, Andrew P Makrigiannis, B Anne Croy
Genetic knockdown (KD) of the mouse Ly49 receptor family is reported to result in infertility despite the presence of zona-enclosed blastocysts in the uterus. Ly49 receptors regulate leukocyte functions particularly Natural Killer (NK) cell functions and are analogous to human killer immunoglobulin-like receptors (KIRs). Histological analyses of gd3.5-4.5 B6.Ly49(KD) uteri identified hatched but retarded blastocysts with pyknotic nuclei, aberrant endometrial crypt formation and impaired uterine lumen closure accompanied by a lack of primary decidualization These data support peri-implantation roles for leukocytes expressing the Ly49 receptor repertoire and may give insight into KIR-based regulation of human infertility...
March 2016: Placenta
Mackenzie L Redhead, Nathália A Portilho, Allison M Felker, Shuhiba Mohammad, Danielle L Mara, B Anne Croy
Mice ablated for the gene encoding the transcription factor Nfil3 lack peripheral natural killer (NK) cells but retain tissue-resident NK cells, particularly in mucosal sites, including virgin uterus. We undertook a time course histological study of implantation sites from syngeneically (Nfil3(-/-)) and allogeneically (BALB/c) mated Nfil3(-/-) females. We also examined implantation sites from Rag2(-/-)Il2rg(-/-) females preconditioned by adoptive transfer of Nfil3(-/-) marrow or uterine cell suspensions to identify the Nfil3(-/-) pregnancy aberrations that could be attributed to nonlymphoid cells...
May 2016: Biology of Reproduction
Gendie E Lash, Hedele Pitman, Hannah L Morgan, Barbara A Innes, Chinedu N Agwu, Judith N Bulmer
Successful remodeling of the uterine spiral arteries is essential for a complication-free pregnancy and is best described in terms of its morphologic features. The molecular mediators and cellular sources of spiral artery remodeling are not known, although a role for uterine leukocytes has been proposed. Immunohistochemical assessment of placental bed biopsies demonstrated uterine NK cells, macrophages, and T lymphocytes in the wall and adventitia of spiral arteries at different stages of remodeling, regardless of the presence of extravillous trophoblast cells...
August 2016: Journal of Leukocyte Biology
Raj Raghupathy, Julia Szekeres-Bartho
Progesterone is indispensable for the maintenance of pregnancy, both via its endocrine effects and its role in creating a favorable immunological environment for the fetus. This review focuses on the immunological effects of progesterone. Progestogens have been shown to have very interesting effects on cytokine production and decidual natural killer (NK) cell activity. The orally-administered progestogen, dydrogesterone, has the ability to modulate cytokine production patterns in a manner that could be conducive to successful pregnancy...
August 1, 2016: Hormone Molecular Biology and Clinical Investigation
Jintang Sun, Meixiang Yang, Yanli Ban, Wenjuan Gao, Bingfeng Song, Yang Wang, Yun Zhang, Qianqian Shao, Beihua Kong, Xun Qu
NK cells accumulate at the maternal-fetal interface (MFI) and play essential roles in maintaining immune tolerance during pregnancy. The mechanisms that facilitate NK cells tolerance to fetal tissue are largely unknown. T cell Ig and mucin domain-containing protein 3 (Tim-3) is a newly defined molecule with essential immunological function in many physiological and pathological processes. Recent study showed that Tim-3 was involved in the regulation of immune tolerance at MFI. However, whether Tim-3 regulates NK cells cytotoxicity toward trophoblasts is unclear...
2016: PloS One
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