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Uterus nk

Stephen J Renaud, Regan L Scott, Damayanti Chakraborty, Mohammad A K Rumi, Michael J Soares
Natural killer (NK) cells are the most prevalent leukocyte population in the uterus during early pregnancy. Natural killer cells contribute to uterine vascular (spiral artery) remodeling in preparation for the increased demand on these vessels later in pregnancy. A second wave of spiral artery modification is directed by invasive trophoblast cells. The significance of the initial wave of NK-cell-mediated vascular remodeling in species exhibiting deep trophoblast invasion such as humans and rats is not known...
January 1, 2017: Biology of Reproduction
Guannan Li, Shan E Ahmed Raza, Nasir M Rajpoot
It has been recently shown that recurrent miscarriage can be caused by abnormally high ratio of number of uterine natural killer (UNK) cells to the number of stromal cells in human female uterus lining. Due to high workload, the counting of UNK and stromal cells needs to be automated using computer algorithms. However, stromal cells are very similar in appearance to epithelial cells which must be excluded in the counting process. To exclude the epithelial cells from the counting process it is necessary to identify epithelial regions...
January 22, 2017: Medical Image Analysis
N C Clark, C A Pru, J K Pru
The uterus is a highly dynamic organ, undergoing dramatic physiological changes during normal cyclicity and pregnancy. Many of these changes involve remodeling of the uterine vasculature in order to provide oxygen and nutrients to the developing embryo/fetus. Vasculogenesis, angiogenesis, vasodilation/vasoconstriction, and vascular permeability are coordinated by a vast network of autocrine, paracrine, and endocrine-signaling factors that derive from a number of cellular sources at the maternal:fetal interface, as well as from tissue outside the uterus...
2017: Progress in Molecular Biology and Translational Science
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...
April 2017: 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
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
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
Vaclav Vetvicka, Antonio Simone Laganà, Francesca Maria Salmeri, Onofrio Triolo, Vittorio Italo Palmara, Salvatore Giovanni Vitale, Vincenza Sofo, Milena Králíčková
PURPOSE: Endometriosis is defined as the presence of endometrial-like endometrial cells, glands and stroma outside the uterus, causing a strong inflammatory-like microenvironment in the affected tissue. This may provoke a breakdown in the peritoneal cavity homeostasis, with the consequent processes of immune alteration, documented by peripheral mononuclear cells recruitment and secretion of inflammatory cytokines in early phases and of angiogenic and fibrogenic cytokines in the late stages of the disease...
November 2016: Archives of Gynecology and Obstetrics
Moriya Gamliel, Karen L Anderson, Richard P Ebstein, Nurit Yirmiya, David Mankuta
Killer-cell immunoglobulin-like receptors (KIRs) are a family of cell surface proteins found on natural killer cells, which are components of the innate immune system. KIRs recognize MHC class I proteins, mainly HLA-C and are further divided into two groups: short-tailed 2/3DS activating receptors and long-tailed 2/3DL inhibitory receptors. Based on the Barker Hypothesis, the origins of illness can be traced back to embryonic development in the uterus, and since KIR:HLA interaction figures prominently in the maternal-fetal interface, we investigated whether specific KIR:HLA combinations may be found in autism spectrum disorders (ASD) children compared with their healthy parents...
2016: Frontiers in Pediatrics
Janine E Melsen, Gertjan Lugthart, Arjan C Lankester, Marco W Schilham
Two human natural killer (NK) cell subsets are usually distinguished, displaying the CD56(dim)CD16(+) and the CD56(bright)CD16(-/+) phenotype. This distinction is based on NK cells present in blood, where the CD56(dim) NK cells predominate. However, CD56(bright) NK cells outnumber CD56(dim) NK cells in the human body due to the fact that they are predominant in peripheral and lymphoid tissues. Interestingly, within the total CD56(bright) NK cell compartment, a major phenotypical and functional diversity is observed, as demonstrated by the discovery of tissue-resident CD56(bright) NK cells in the uterus, liver, and lymphoid tissues...
2016: Frontiers in Immunology
Hoda Bahrami, Reza Roozafzoon, Zinat Ghanbari, Neda Jegargooshe, Parvaneh Jafari, Mohammad Nazari, Saeed Heidari-Keshel
BACKGROUND: Endometriosis is a commonly-encountered gynecological disease characterized by the presence of endometrial glandular and stromal cells outside of the uterus. Several studies have been conducted on endometriosis, however its molecular mechanism and pathogenesis are still not completely clear. The role of ELAM-1 gene in mediating the adhesion of tumor cells to endothelial cells by binding to ELAM-1 ligands expressed by eosinophils, neutrophils, monocytes, natural killer cell effectors, T lymphocyte cells, and cancer (progenitor/stem) cells is well studied...
April 2017: Minerva Ginecologica
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
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
Selma Boulenouar, Jean-Marc Doisne, Amanda Sferruzzi-Perri, Louise M Gaynor, Jens Kieckbusch, Elisa Balmas, Hong Wa Yung, Shagayegh Javadzadeh, Léa Volmer, Delia A Hawkes, Keli Phillips, Hugh J M Brady, Abigail L Fowden, Graham J Burton, Ashley Moffett, Francesco Colucci
Uterine NK cells are innate lymphoid cells (ILC) that populate the uterus and expand during pregnancy, regulating placental development and fetal growth in humans and mice. We have recently characterized the composition of uterine ILCs (uILCs), some of which require the transcription factor NFIL3, but the extent to which NFIL3-dependent cells support successful reproduction in mice is unknown. By mating Nfil3 (-/-) females with wild-type males, here we show the effects of NFIL3 deficiency in maternal cells on both the changes in uILCs during pregnancy and the downstream consequences on reproduction...
2016: Frontiers in Immunology
Kirstin L Parkin, Asgerally T Fazleabas
Endometriosis is a chronic inflammatory disease characterized by the growth of endometrial glands and stroma outside of the uterus. The disease affects approximately 10-15% of women of reproductive age and presents with clinical symptoms of pelvic pain and infertility. Changes in the leukocyte populations within the ectopic tissue and eutopic endometrium have been reported, and data suggest these alterations contribute to the pathology and symptoms of the disease. In this review, we discussed differences when comparing uterine NK cells and regulatory T cells within the eutopic endometrium between patients with endometriosis and healthy patients, and how these differences relate to implantation failure and/or decreased clearance of menstrual tissue in patients with the disease...
March 2016: American Journal of Reproductive Immunology: AJRI
Kerrilyn R Diener, Sarah A Robertson, John D Hayball, Erin L Lousberg
Investigating immune cell populations within various reproductive tissues commonly utilises flow cytometric methods. With advances in fluorophore technology and equipment capabilities, multiple cell types from a single tissue sample can be identified by using different combinations of cell surface markers to distinguish specific cell populations. Here a protocol optimized for mouse uterine tissue was used to show the proportional changes in dendritic cells, monocyte/macrophages, T and B cells, NK and NK T cells, and the granulocytes, neutrophils and eosinophils at each of the four stages of the estrous cycle...
February 2016: Journal of Reproductive Immunology
Jens Kieckbusch, Elisa Balmas, Delia A Hawkes, Francesco Colucci
Maternal immune cells are an integral part of reproduction, but how they might cause pregnancy complications remains elusive. Macrophages and their dual function in inflammation and tissue repair are thought to play key yet undefined roles. Altered perinatal growth underpins adult morbidity, and natural killer (NK) cells may sustain fetal growth by establishing the placental blood supply. Using a mouse model of genetic inactivation of PI3K p110δ, a key intracellular signaling molecule in leukocytes, we show that p110δ regulates macrophage dynamics and NK-cell-mediated arterial remodeling...
December 29, 2015: Cell Reports
Jens Kieckbusch, Louise M Gaynor, Francesco Colucci
The placenta mediates the exchange of factors such as gases and nutrients between mother and fetus and has specific demands for supply of blood from the maternal circulation. The maternal uterine vasculature needs to adapt to this temporary demand and the success of this arterial remodeling process has implications for fetal growth. Cells of the maternal immune system, especially natural killer (NK) cells, play a critical role in this process. Here we describe a method to assess the degree of remodeling of maternal spiral arteries during mouse pregnancy...
December 5, 2015: Journal of Visualized Experiments: JoVE
Frank T Spradley, Ana C Palei, Joey P Granger
Preeclampsia (PE) is characterized by hypertension occurring after the twentieth week of pregnancy. It is a significant contributor to maternal and perinatal morbidity and mortality in developing countries and its pervasiveness is increasing within developed countries including the USA. However, the mechanisms mediating the pathogenesis of this maternal disorder and its rising prevalence are far from clear. A major theory with strong experimental evidence is that placental ischemia, resulting from inappropriate remodeling and widening of the maternal spiral arteries, stimulates the release of soluble factors from the ischemic placenta causing maternal endothelial dysfunction and hypertension...
November 12, 2015: Biomolecules
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