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uterine nk cells

Binqing Fu, Haiming Wei
During early pregnancy, an orchestrated evolutionary maternal adaption toward tolerance of the semiallogeneic fetus is required to ensure decidualization and early embryo development. Remodeling of the immune system involves natural killer cells (NKs), macrophages, T cells and dendritic cells (DCs) altering the microenvironment in the deciduas. In particular, a unique population of NK cells with a CD56(bright)CD16(-) phenotype in the decidua has been proposed to play a key role in the maternal adaptation to pregnancy...
November 29, 2016: Science China. Life Sciences
R J Kuon, K Vomstein, M Weber, F Müller, C Seitz, S Wallwiener, T Strowitzki, E Schleussner, U R Markert, V Daniel, B Toth
Peripheral and uterine NK cells (pNK, uNK) can be distinguished according to their receptor expression. Recent studies indicate an association of elevated pNK and uNK with recurrent miscarriage (RM). This study aimed to analyze pNK and uNK in patients with RM and healthy controls. Out of n=590 RM patients screened according to a standard diagnostic protocol, n=268 couples with ≥3 consecutive RM were identified. Subgroups consisted of n=151 primary RM (pRM), n=85 secondary RM (sRM), n=32 tertiary RM (tRM) and n=42 healthy controls...
November 6, 2016: Journal of Reproductive Immunology
Chao-Yang Meng, Zhong-Yin Li, Wen-Ning Fang, Zhi-Hui Song, Dan-Dan Yang, Dan-Dan Li, Ying Yang, Jing-Pian Peng
Cytochrome P450 26A1 (CYP26A1) has a spatiotemporal expression pattern in the uterus, with a significant increase in mRNA and protein levels during peri-implantation. Inhibiting the function or expression of CYP26A1 can cause pregnancy failure, suggesting an important regulatory role of CYP26A1 in the maintenance of pregnancy. However, little is known about the exact mechanism involved. In this study, using a pCR3.1-cyp26a1 plasmid immunization mouse model and a Cyp26a1-MO (Cyp26a1-specific antisense oligos) knockdown mouse model, we report that the number of Dolichos biflorus agglutinin (DBA) lectin-positive uterine natural killer (uNK) cells was reduced in pCR3...
November 17, 2016: Journal of Cellular and Molecular Medicine
Philippa R Kennedy, Olympe Chazara, Lucy Gardner, Martin A Ivarsson, Lydia E Farrell, Shiqiu Xiong, Susan E Hiby, Francesco Colucci, Andrew M Sharkey, Ashley Moffett
Tissue-specific NK cells are abundant in the pregnant uterus and interact with invading placental trophoblast cells that transform the maternal arteries to increase the fetoplacental blood supply. Genetic case-control studies have implicated killer cell Ig-like receptor (KIR) genes and their HLA ligands in pregnancy disorders characterized by failure of trophoblast arterial transformation. Activating KIR2DS1 or KIR2DS5 (when located in the centromeric region as in Africans) lower the risk of disorders when there is a fetal HLA-C allele carrying a C2 epitope...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Xiao-Hui Hu, Mao-Xing Tang, Gil Mor, Ai-Hua Liao
Successful pregnancy relies on the accurate regulation of the maternal-fetal immune system. Without enough tolerance in the uterine microenvironment, the mother and the hemiallogeneic fetus could not peacefully coexist. T cell immunoglobulin and mucin domain (Tim)-3 is a molecule originally regarded as to be expressed on terminally differentiated IFN-γ expressing CD4(+) T cells (Th1). The engagement of Tim-3 with its ligand, galectin-9 (Gal-9) could induce the exhaustion or apoptosis of effector T cells, and thus might regulate the tolerance...
October 20, 2016: Journal of Reproductive Immunology
Yu-Han Meng, Xiao-Hui Zhu, Li-Ying Yan, Yan Zhang, Hong-Yan Jin, Xi Xia, Rong Li, Jie Qiao
INTRODUCTION: The successful pregnancy depends on maternal immune tolerance against the fetus. It has been reported that MSCs (mesenchymal stem cells) could play a regulatory role on immune cells such as CD4(+)T cells, macrophages and NK cells, but their effect on recurrent miscarriage is unknown. STUDY DESIGN: In a prospective study, the abortion-prone (CBA/J × DBA/2) H-2(d) × H-2(k) mice were utilized. Female CBA/J mice (8-10 weeks old) were injected with vehicle or MSCs via tail vein or uterine horns, and 14 days later, they were mated with DBA/2 males for the following experiments...
November 2016: Placenta
Ashley Moffett, Olympe Chazara, Francesco Colucci, Martin H Johnson
A distinctive type of (uterine) natural killer (NK) cell is present in the uterine decidua during the period of placental formation. Uterine NK cells express members of the killer immunoglobulin-like receptor (KIR) family that bind to parental HLA-C molecules on the invading placental trophoblast cells. The maternal KIR genes and their fetal ligands are highly variable, so different KIR/HLA-C genetic combinations occur in each pregnancy. Some women only possess inhibitory KIR genes, whereas other women also express activating KIR genes...
September 5, 2016: Reproductive Biomedicine Online
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
Heather Yvonne Small, Ryszard Nosalski, Hannah Morgan, Elisabeth Beattie, Tomasz J Guzik, Delyth Graham, Christian Delles
Women with chronic hypertension are at increased risk of maternal and fetal morbidity and mortality. We have previously characterized the stroke-prone spontaneously hypertensive rat (SHRSP) as a model of deficient uterine artery function and adverse pregnancy outcome compared with the control Wistar-Kyoto. The activation of the immune system plays a role in hypertension and adverse pregnancy outcome. Therefore, we investigated the role of tumor necrosis factor-α in the SHRSP phenotype in an intervention study using etanercept (0...
November 2016: Hypertension
Michaela Golic, Friedrich C Luft, Ralf Dechend
No abstract text is available yet for this article.
November 2016: Hypertension
Sofie Perdu, Barbara Castellana, Yoona Kim, Kathy Chan, Lauren DeLuca, Alexander G Beristain
Over one-fifth of North American women of childbearing age are obese, putting these women at risk for a variety of detrimental chronic diseases. In addition, obesity increases the risk for developing major complications during pregnancy. The mechanisms by which obesity contributes to pregnancy complications and loss remain unknown. Increasing evidence indicates that obesity results in major changes to adipose tissue immune cell composition and function; whether or not obesity also affects immune function in the uterus has not been explored...
July 21, 2016: JCI Insight
Mostafa Fouad Gomaa, Ihab Fouad Serag Eldeen, Laila Aly Farid, Mourad Mohey Eldeen El-Saeed, Ahmed Mohammed Abas, Nahla Mohammad Aawd
OBJECTIVE: To compare between uterine natural killer (uNK) cells in the placental samples of preterm birth and term labor. STUDY DESIGN: Two-arm case-control study. This study included 60 participants divided into two groups. The first group included 30 cases of idiopathic spontaneous preterm labor and the other group included 30 women who delivered by a spontaneous term vaginal delivery and with no history of previous preterm labor. RESULT(S): There were no CD16(-) CD56(bright) uNK cells in either groups; CD16(+) CD56(dim) uNK cells were present in only 1 case out of 30 term delivery placentae (3...
September 5, 2016: Journal of Maternal-fetal & Neonatal Medicine
Michaela Golic, Nadine Haase, Florian Herse, Anika Wehner, Lisbeth Vercruysse, Robert Pijnenborg, Andras Balogh, Per Christian Saether, Erik Dissen, Friedrich C Luft, Lukasz Przybyl, Joon-Keun Park, Patji Alnaes-Katjavivi, Anne Cathrine Staff, Stefan Verlohren, Wolfgang Henrich, Dominik N Muller, Ralf Dechend
Uterine natural killer cells are important for uteroplacental development and pregnancy maintenance. Their role in pregnancy disorders, such as preeclampsia, is unknown. We reduced the number of natural killer cells by administering rabbit anti-asialo GM1 antiserum in an established rat preeclamptic model (female human angiotensinogen×male human renin) and evaluated the effects at the end of pregnancy (day 21), compared with preeclamptic control rats receiving normal rabbit serum. In 100% of the antiserum-treated, preeclamptic rats (7/7), we observed highly degenerated vessel cross sections in the mesometrial triangle at the end of pregnancy...
October 2016: Hypertension
H Small, R Nosalski, H Morgan, E Beattie, T Guzik, D Graham, C Delles
OBJECTIVE: Impaired vascular remodelling has been extensively studied in pre-eclampsia but little is known about adaptation of the cardiovascular (CV) system to pregnancy in women with chronic hypertension. We have previously characterised the stroke prone spontaneously hypertensive rat (SHRSP) as a model of deficient uterine artery remodelling and identified an increase in pro-inflammatory TNF α relative to the normotensive WKY strain during pregnancy. DESIGN AND METHOD: SHRSP were treated with etanercept (0...
September 2016: Journal of Hypertension
Bruno Zavan, Eliana Martins De Almeida, Évila da Silva Lopes Salles, Andréa Mollica do Amarante-Paffaro, Valdemar Antonio Paffaro
INTRODUCTION: Although uterine Natural Killer (uNK) cells have cytoplasmic granules rich in perforin and granzymes, these cells do not degranulate in normal pregnancy. DBA lectin(+) uNK cells produce angiogenic factors which stimulate remodeling of uterine arterioles to increase blood flow within the growing feto-placental unit. We sought to investigate the importance of COX-2 on mouse pregnancy inoculated with Gram-negative bacteria Lipopolysaccharide (LPS) by treating with a selective COX-2 inhibitor (nimesulide)...
August 2016: Placenta
Heloisa M Rutigliano, Aaron J Thomas, Amanda Wilhelm, Benjamin R Sessions, Brady A Hicks, Donald H Schlafer, Kenneth L White, Christopher J Davies
Trophoblast cells from bovine somatic cell nuclear transfer (SCNT) conceptuses express major histocompatibility complex class I (MHC-I) proteins early in gestation, and this may be one cause of the significant first-trimester embryonic mortality observed in these pregnancies. MHC-I homozygous-compatible (n = 9), homozygous-incompatible (n = 8), and heterozygous-incompatible (n = 5) SCNT pregnancies were established. The control group consisted of eight pregnancies produced by artificial insemination. Uterine and placental samples were collected on Day 35 ± 1 of pregnancy, and expression of MHC-I, leukocyte markers, and cytokines were examined by immunohistochemistry...
August 2016: Biology of Reproduction
Kohei Fuchinoue, Atsushi Fukui, Hitomi Chiba, Mai Kamoi, Ayano Funamizu, Ayako Taima, Rie Fukuhara, Hideki Mizunuma
AIM: Recently, NK22 cells, a subset of interleukin (IL)-22-producing natural killer (NK) cells, were identified. We have previously reported the higher percentage of NK22 cells in women suffering recurrent pregnancy loss (RPL). Moreover, we have also reported lower expression of NKp46, a kind of natural cytotoxicity receptor (NCR), on NK cells and the changes of NK cell producing cytokines in women who experience RPL. NK22 cells express NCRs, such as NKp44 or NKp46. Retinoid-related orphan receptor γt (RORγt) is known as a regulator of NK22 cells; however, in NK22 cells of peripheral blood (PB) and the uterine endometrium (UE), the relationship between NCRs and RORγt is unclear...
July 3, 2016: Journal of Obstetrics and Gynaecology Research
Roberto Marci, Valentina Gentili, Daria Bortolotti, Giuseppe Lo Monte, Elisabetta Caselli, Silvia Bolzani, Antonella Rotola, Dario Di Luca, Roberta Rizzo
To elucidate the roles of human herpesvirus (HHV)-6 primary unexplained infertile women, a prospective randomized study was conducted on a cohort of primary unexplained infertile women and a cohort of control women, with at least one successful pregnancy. HHV-6 DNA was analyzed and the percentage and immune-phenotype of resident endometrial Natural Killer (NK) cells, as the first line of defense towards viral infections, was evaluated in endometrial biopsies. Cytokine levels in uterine flushing samples were analyzed...
2016: PloS One
Jun Tanaka, Akira Kitashoji, Yuki Fukunaga, Junichi Kashihara, Atsushi Nakano, Akihito Kamizono
Recurrent pregnancy loss (RPL), which mostly is of unknown etiology (unexplained RPL, uRPL), is defined as three or more consecutive spontaneous abortions. Some women with uRPL display a higher fraction and cytotoxicity of natural killer (NK) cells in the periphery and endometrium. Therefore, some uRPL cases have been explained by autoimmune abnormalities. The efficacy of intravenous immunoglobulin (IVIg) for uRPL has been confirmed in several clinical trials; however, its mechanism remains unknown, mainly because the abortion mechanism remains to be elucidated...
August 2016: Biology of Reproduction
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
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