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https://www.readbyqxmd.com/read/28815854/expression-of-natural-cytotoxicity-receptors-and-cytokine-production-on-endometrial-natural-killer-cells-in-women-with-recurrent-pregnancy-loss-or-implantation-failure-and-the-expression-of-natural-cytotoxicity-receptors-on-peripheral-blood-natural-killer-cells
#1
Atsushi Fukui, Ayano Funamizu, Rie Fukuhara, Hiroaki Shibahara
AIM: Natural cytotoxicity receptors (NCR) are unique markers that regulate natural killer (NK) cell cytotoxicity and cytokine production. In this study, we investigated the expression of NCR (NKp46, NKp44, and NKp30) and cytokine production in NK cells derived from the uterine endometrium of women with recurrent pregnancy loss (RPL). We also investigated the expression of NCR in peripheral blood NK cells in pregnant women with and without a history of RPL. METHODS: The expression of NCR (NKp46, NKp44, and NKp30) in NK cells (CD56(dim) and CD56(bright) ) in the uterine endometrium was analyzed using 3-color flow cytometry...
August 17, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28794456/activated-nk-cells-cause-placental-dysfunction-and-miscarriages-in-fetal-alloimmune-thrombocytopenia
#2
Issaka Yougbaré, Wei-She Tai, Darko Zdravic, Brigitta Elaine Oswald, Sean Lang, Guangheng Zhu, Howard Leong-Poi, Dawei Qu, Lisa Yu, Caroline Dunk, Jianhong Zhang, John G Sled, Stephen J Lye, Jelena Brkić, Chun Peng, Petter Höglund, B Anne Croy, S Lee Adamson, Xiao-Yan Wen, Duncan J Stewart, John Freedman, Heyu Ni
Miscarriage and intrauterine growth restriction (IUGR) are devastating complications in fetal/neonatal alloimmune thrombocytopenia (FNAIT). We previously reported the mechanisms for bleeding diatheses, but it is unknown whether placental, decidual immune cells or other abnormalities at the maternal-fetal interface contribute to FNAIT. Here we show that maternal immune responses to fetal platelet antigens cause miscarriage and IUGR that are associated with vascular and immune pathologies in murine FNAIT models...
August 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28781765/up-and-down-immunity-of-pregnancy-in-humans
#3
REVIEW
Philippe Le Bouteiller, Armand Bensussan
One part of the human placenta in early pregnancy is particularly important for local immunity: the decidua basalis, which is transformed endometrium located at the site of embryo implantation . This placental bed tissue contains both maternal uterine immune cells, including decidual natural killer (NK) cells, the dominant leukocyte population exhibiting a unique phenotype, and fetal extravillous trophoblast which comes into direct contact with maternal decidual cells . To establish a successful placental development and healthy pregnancy outcome, the maternal immune system must tolerate paternal antigens expressed by trophoblast cells yet remain efficient for clearing any local pathogen infection...
2017: F1000Research
https://www.readbyqxmd.com/read/28771871/predicting-nk-cell-subsets-using-gene-expression-levels-in-peripheral-blood-and-endometrial-biopsy-specimens
#4
Michael L Davies, Svetlana V Dambaeva, Dimantha Katukurundage, Miroslava Repak, Alice Gilman-Sachs, Joanne Kwak-Kim, Kenneth D Beaman
PROBLEM: In molecular analysis of tissue biopsy specimens, one crucial aspect is characterization of immune cell populations. This is especially important for evaluation of uterine receptivity by assessing levels of lymphocyte populations including CD56(bright) CD16- uterine NK cells and CD56(dim) CD16+ conventional NK cells. Our objective was to investigate whether measuring total RNA transcripts from a tissue specimen would accurately reflect immune cell levels and be a new technique to assess immune cell subsets...
August 3, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28727763/loss-of-receptor-activity-modifying-protein-2-in-mice-causes-placental-dysfunction-and-alters-pth1r-regulation
#5
Mahita Kadmiel, Brooke C Matson, Scott T Espenschied, Patricia M Lenhart, Kathleen M Caron
Receptor activity-modifying protein 2 (Ramp2) is a single-pass transmembrane protein that heterodimerizes with several family B G-protein coupled receptors to alter their function. Ramp2 has been primarily characterized in association with calcitonin receptor-like receptor (Calcrl, CLR), forming the canonical receptor complex for the endocrine peptide adrenomedullin (Adm, AM). However, we previously demonstrated that Ramp2+/- female mice display a constellation of endocrine-related phenotypes that are distinct from those of Adm+/- and Calcrl+/- mice, implying that RAMP2 has physiological functions beyond its canonical complex...
2017: PloS One
https://www.readbyqxmd.com/read/28695287/the-role-of-kir-and-hla-interactions-in-pregnancy-complications
#6
REVIEW
Francesco Colucci
Combinations of KIR and HLA genes associate with pregnancy complications as well as with many other clinical scenarios. Understanding how certain KIR and HLA genes influence the biology of a disease is, however, a formidable challenge. These are the two most variable gene families in the human genome. Moreover, the biology of a disease is best understood by studying the cells of the affected tissue. Natural Killer (NK) cells express KIR and are the most abundant leukocytes in the uterus. Most of our knowledge of NK cells is based on what we have learned from cells isolated from blood, but these are different from their tissue resident counterparts, including uterine NK (uNK) cells...
July 10, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28693893/emerging-role-for-dysregulated-decidualization-in-the-genesis-of-preeclampsia
#7
Kirk P Conrad, Maria Belen Rabaglino, Emiel D Post Uiterweer
In normal human placentation, uterine invasion by trophoblast cells and subsequent spiral artery remodeling depend on cooperation among fetal trophoblasts and maternal decidual, myometrial, immune and vascular cells in the uterine wall. Therefore, aberrant function of anyone or several of these cell-types could theoretically impair placentation leading to the development of preeclampsia. Because trophoblast invasion and spiral artery remodeling occur during the first half of pregnancy, the molecular pathology of fetal placental and maternal decidual tissues following delivery may not be informative about the genesis of impaired placentation, which transpired months earlier...
June 9, 2017: Placenta
https://www.readbyqxmd.com/read/28670317/safeguarding-of-fetal-growth-by-mast-cells-and-natural-killer-cells-deficiency-of-one-is-counterbalanced-by-the-other
#8
Nicole Meyer, Katja Woidacki, Marcus Maurer, Ana Claudia Zenclussen
Uterine natural killer cells (uNKs) and mast cells (uMCs) are of crucial importance for spiral artery (SA) remodeling and placentation. Mice deficient for both NKs and MCs including uNKs and uMCs show markedly impaired SA remodeling and their fetuses are growth-retarded. In contrast, the absence of either NKs or MCs results in only minor impairment. This suggests that uNKs can compensate for the effects of uMCs on SA remodeling and vice versa. To test this hypothesis, we assessed uNK numbers in uMC-deficient mice as well as uMC numbers in uNK-depleted mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28653669/dnk-cells-facilitate-the-interaction-between-trophoblastic-and-endothelial-cells-via-vegf-c-and-hgf
#9
Liyang Ma, Guanlin Li, Guangming Cao, Yuchun Zhu, Mei-Rong Du, Yangyu Zhao, Hao Wang, Yanlei Liu, Yanyan Yang, Yu-Xia Li, Da-Jin Li, Huixia Yang, Yan-Ling Wang
Decidual NK (dNK) cells, identified as CD56(bright)CD16(-)CD3(-), account for ~70% of lymphocytes within the uterine wall during early pregnancy. Accumulating evidence suggests that tight interactions between placental trophoblasts and dNK cells are critical for trophoblast cell differentiation. However, the underlying mechanism remains to be explored in detail. In the present study, conditioned medium (CM) was collected from cultured primary human dNK cells. Primary cytotrophoblasts (CTBs) or the human trophoblast cell line HTR8/SVneo was treated with dNK-CM and co-cultured with human umbilical vein endothelial cells (HUVECs) in a three-dimensional Matrigel scaffold, and the formation of tube structures was dynamically monitored with live cell imaging...
June 9, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28639334/uterine-natural-killer-cells-in-patients-with-idiopathic-recurrent-miscarriage
#10
Ruben-J Kuon, Maja Weber, Julia Heger, Isabel Santillán, Kilian Vomstein, Christin Bär, Thomas Strowitzki, Udo R Markert, Bettina Toth
PROBLEM: Uterine natural killer (uNK) cells are major players during implantation and early pregnancy. The aim of our study was to analyze uNK cell concentration in the endometrium of idiopathic recurrent miscarriage (iRM) patients and fertile controls. METHOD OF STUDY: Out of n=130 couples with ≥3 consecutive, clinical RM screened according to a standardized diagnostic protocol, n=58 patients with iRM were identified. Endometrial biopsies were investigated in patients and n=17 fertile women (controls) via immunohistochemistry...
June 21, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28633489/effects-of-early-pregnancy-on-uterine-lymphocytes-and-endometrial-expression-of-immune-regulatory-molecules-in-dairy-heifers1
#11
Sreelakshmi Vasudevan, Manasi M Kamat, Sadhat S Walusimbi, Joy L Pate, Troy L Ott
Natural killer (NK) cells are essential for establishment of human and rodent pregnancies. The function of these and other cytotoxic T cells (CTL) is controlled by stimulatory and inhibitory signaling. A role for cytotoxic cells during early pregnancy in cattle has not been described, but regulation of their function at the fetal-maternal interface is thought to be critical for conceptus survival. The hypothesis that the relative abundance of CTL and expression of inhibitory signaling molecules is increased by the conceptus during early pregnancy was tested...
June 19, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28620462/immunoprofiling-of-human-uterine-mast-cells-identifies-three-phenotypes-and-expression-of-er%C3%AE-and-glucocorticoid-receptor
#12
Bianca De Leo, Arantza Esnal-Zufiaurre, Frances Collins, Hilary O D Critchley, Philippa T K Saunders
Background: Human mast cells (MCs) are long-lived tissue-resident immune cells characterised by granules containing the proteases chymase and/or tryptase. Their phenotype is modulated by their tissue microenvironment. The human uterus has an outer muscular layer (the myometrium) surrounding the endometrium, both of which play an important role in supporting a pregnancy. The endometrium is a sex steroid target tissue consisting of epithelial cells (luminal, glandular) surrounded by a multicellular stroma, with the latter containing an extensive vascular compartment as well as fluctuating populations of immune cells that play an important role in regulating tissue function...
2017: F1000Research
https://www.readbyqxmd.com/read/28588205/human-uterine-lymphocytes-acquire-a-more-experienced-and-tolerogenic-phenotype-during-pregnancy
#13
Dorien Feyaerts, Marilen Benner, Bram van Cranenbroek, Olivier W H van der Heijden, Irma Joosten, Renate G van der Molen
Pregnancy requires a delicate immune balance that nurtures the allogeneic fetus, while maintaining reactivity against pathogens. Despite increasing knowledge, data is lacking on the transition of pre-pregnancy endometrial lymphocytes to a pregnancy state. Here, we immunophenotyped lymphocytes from endometrium (MMC), term decidua parietalis (DPMC), and PBMC for direct comparison. We found that the immune cell composition of MMC and DPMC clearly differ from each other, with less NK-cells, and more NKT-cells and T-cells in DPMC...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28578177/the-impact-of-uterine-immaturity-on-obstetrical-syndromes-during%C3%A2-adolescence
#14
Ivo Brosens, Joanne Muter, Caroline E Gargett, Patrick Puttemans, Giuseppe Benagiano, Jan J Brosens
Pregnant nulliparous adolescents are at increased risk, inversely proportional to their age, of major obstetric syndromes, including preeclampsia, fetal growth restriction, and preterm birth. Emerging evidence indicates that biological immaturity of the uterus accounts for the increased incidence of obstetrical disorders in very young mothers, possibly compounded by sociodemographic factors associated with teenage pregnancy. The endometrium in most newborns is intrinsically resistant to progesterone signaling, and the rate of transition to a fully responsive tissue likely determines pregnancy outcome during adolescence...
May 31, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28577615/maternal-allo-recognition-of-the-fetus
#15
REVIEW
Ashley Moffett, Olympe Chazara, Francesco Colucci
Immunological adjustments are needed to accommodate the close contact between two genetically different individuals, the mother and her baby, during mammalian pregnancy. Contact occurs between fetal somatic or placental cells that enter the maternal systemic circulation or between uterine immune cells and the invading extravillous trophoblast. Here we discuss two main types of maternal allo-recognition of the fetus. One depends on avoidance of maternal T cells recognizing and responding to paternally-derived non-self human leukocyte antigens class I and class I allotypes...
June 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28566515/a-microfluidics-assay-to-study-invasion-of-human-placental-trophoblast-cells
#16
Yassen Abbas, Carolin Melati Oefner, William J Polacheck, Lucy Gardner, Lydia Farrell, Andrew Sharkey, Roger Kamm, Ashley Moffett, Michelle L Oyen
Pre-eclampsia, fetal growth restriction and stillbirth are major pregnancy disorders throughout the world. The underlying pathogenesis of these diseases is defective placentation characterized by inadequate invasion of extravillous placental trophoblast cells into the uterine arteries. How trophoblast invasion is controlled remains an unanswered question but is influenced by maternal uterine immune cells called decidual natural killer cells. Here, we describe an in vitro microfluidic invasion assay to study the migration of primary human trophoblast cells...
May 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28526846/nk-cell-derived-il-10-is-critical-for-dc-nk-cell-dialogue-at-the-maternal-fetal-interface
#17
Sandra M Blois, Nancy Freitag, Irene Tirado-González, Shi-Bin Cheng, Markus M Heimesaat, Stefan Bereswill, Matthias Rose, Melanie L Conrad, Gabriela Barrientos, Surendra Sharma
DC-NK cell interactions are thought to influence the development of maternal tolerance and de novo angiogenesis during early gestation. However, it is unclear which mechanism ensures the cooperative dialogue between DC and NK cells at the feto-maternal interface. In this article, we show that uterine NK cells are the key source of IL-10 that is required to regulate DC phenotype and pregnancy success. Upon in vivo expansion of DC during early gestation, NK cells expressed increased levels of IL-10. Exogenous administration of IL-10 was sufficient to overcome early pregnancy failure in dams treated to achieve simultaneous DC expansion and NK cell depletion...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28523429/kir-lilrb-and-their-ligands-genes-as-potential-biomarkers-in-recurrent-implantation-failure
#18
REVIEW
Izabela Nowak, Karolina Wilczyńska, Jacek R Wilczyński, Andrzej Malinowski, Paweł Radwan, Michał Radwan, Piotr Kuśnierczyk
Reproductive failure in humans is a very important social and economic problem, because nowadays women decide to conceive later in life and delay motherhood. Unfortunately, with increasing age they have less chance for natural fertilization and maintenance of pregnancy. Many of them need assisted reproductive technology. Approximately 10% of women after in vitro fertilization-embryo transfers experience recurrent implantation failure (RIF). Multiple factors may contribute to RIF, including oocyte and sperm quality, parental chromosomal anomalies, genetic or metabolic abnormalities of the embryo, poor uterine receptivity, immunological disturbances in the implantation site, and some gynecologic pathologies such as endometriosis, uterine fibroids, hydrosalpinx and endometrial polyps...
May 18, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28501368/contribution-of-immunology-to-implantation-failure-of-euploid-embryos
#19
REVIEW
Jason M Franasiak, Richard T Scott
Outcomes in assisted reproduction have seen marked improvement. With increased ability in the embryology laboratory to use extended embryo culture which in turn enables other selective techniques, such as trophectoderm biopsy and comprehensive chromosome screening, the chance of success per embryo transfer is increased. However, even the selection of a euploid blastocyst, which selects out many embryonic factors, does not yield successful implantation and ultimately delivery in all cases. Among the factors that affect implantation failure of apparently reproductively competent embryos, the immune system has been perhaps both the most plausible and the most debated...
June 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28501365/why-natural-killer-cells-are-not-enough-a-further-understanding-of-killer-immunoglobulin-like-receptor-and-human-leukocyte-antigen
#20
REVIEW
Diana Alecsandru, Juan A García-Velasco
The immune system's role in recurrent reproductive failure is a controversial issue in assisted reproduction. Most studies into immune system implication in reproduction have focused on finding markers of peripheral blood and less on the uterine environment. Peripheral blood natural killer cells have become an "immune study core" for women with recurrent miscarriage or recurrent implantation failure, based on the mistaken notion that they cause reproductive failure by killing or "rejecting" the embryo. Maternal-fetal tolerance begins at the uterine level, so successful adaptation to the fetus occurs after a complicated process...
June 2017: Fertility and Sterility
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