Review: Functional role of uterine natural killer (uNK) cells in human early pregnancy decidua (original) (raw)
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Science in China Series C: Life Sciences, 2008
VEGF-A mRNA, but not Ang2 mRNA, in isolated uNK cells in human decidua of the first-trimester gestation by combination of LCM and Nested-PCR. Our study indicated that uNK cells, through expressing VEGF-A, may play an important role in the angiogenic response at the time of human decidualization and early placenta development. uterine natural killer cells, decidua, angiogenesis, VEGF, Ang2
Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstétrique et gynécologie du Canada : JOGC, 2008
Adequate invasion of the human placenta during the first weeks of pregnancy is a critical step in ensuring both fetal and maternal health. A rapidly expanding body of evidence suggests that decidual natural killer (dNK) cells, a distinct population of CD56brightCD16- lymphocytes, are key regulators of this complex process. Experiments using murine models and in vitro evidence using human tissue cultures suggest that dNK cells modulate extravillous trophoblast (EVT) invasion and remodelling of maternal spiral arteries via both contact-dependent and contact-independent mechanisms. In addition, the differential expression of surface receptors by dNK cells may have a role in determining reproductive success through modulation of the maternal immune system at the time of implantation and placentation. The roles of cytokines, chemokines, and growth factors secreted by dNK cells and their influence on EVT migration, invasion, and pseudovasculogenesis are of particular interest. We reviewed...
The Journal of Pathology, 2012
During human pregnancy, natural killer (NK) cells accumulate in the maternal decidua, but their specific roles remain to be determined. Decidual NK (dNK) cells are present during trophoblast invasion and uterine spiral artery remodelling. These events are crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Remodelling of spiral arteries is impaired in the dangerous pregnancy complication pre-eclampsia. We studied dNK cells isolated from pregnancies at 9-14 weeks' gestation, screened by uterine artery Doppler ultrasound to determine resistance indices which relate to the extent of spiral artery remodelling. dNK cells were able to promote the invasive behaviour of fetal trophoblast cells, partly through HGF. Cells isolated from pregnancies with higher resistance indices were less able to do this and secreted fewer pro-invasive factors.
Uterine natural killer cells and successful pregnancy: from mouse experiments to human physiology
Exploration of Immunology
Uterine natural killer (uNK) cells, a specific type of natural killer (NK) cells, are important cells at the foeto-maternal interface in humans as well as in mice. uNK cells are part of the innate lymphoid cells group 1. Especially in the mouse, but also in the rat, many in vivo studies have been performed to evaluate the role of uNK cells in placental development. These studies have shown that uNK cells are not indispensable to pregnancy, but that they play an important role in optimal decidual angiogenesis in early pregnancy, trophoblast invasion and spiral artery remodelling in the mouse placenta. Based on the mouse studies, various in vitro studies, as well as immunohistological studies of the human placenta from elective abortions, have shown that uNK cells have similar functions in the human placenta. In the present narrative review, the role of the uNK cells in the development of the mouse and rat placenta will be discussed first. Thereafter, studies on the role of human uNK ...
2015
Adequate invasion of the human placenta during the first weeks of pregnancy is a critical step in ensuring both fetal and maternal health. A rapidly expanding body of evidence suggests that decidual natural killer (dNK) cells, a distinct population of CD56brightCD16- lymphocytes, are key regulators of this complex process. Experiments using murine models and in vitro evidence using human tissue cultures suggest that dNK cells modulate extravillous trophoblast (EVT) invasion and remodelling of maternal spiral arteries via both contact-dependent and contact-independent mechanisms. In addition, the differential expression of surface receptors by dNK cells may have a role in determining reproductive success through modulation of the maternal immune system at the time of implantation and placentation. The roles of cytokines, chemokines, and growth
Uterine natural killer cells initiate spiral artery remodeling in human pregnancy
The FASEB Journal, 2012
Uterine spiral artery remodeling is required for successful human pregnancy; impaired remodeling is associated with pregnancy complications, including late miscarriage, preeclampsia, and fetal growth restriction. The molecular triggers of remodeling are not known, but it is now clear that there are "trophoblastindependent" and "trophoblast-dependent" stages. Uterine natural killer (uNK) cells are abundant in decidualized endometrium in early pregnancy; they surround spiral arteries and secrete a range of angiogenic growth factors. We hypothesized that uNK cells mediate the initial stages of spiral artery remodeling. uNK cells and extravillous trophoblast (EVT) cells were isolated from early pregnancy decidua and placenta. Chorionic plate arteries from full-term placentas and spiral arteries from nonpregnant myometrium were cultured with angiogenic growth factors or conditioned medium (CM) from uNK cells or EVT or uNK cell/EVT cocultures. In both vessel models, uNK cell CM induced disruption of vascular smooth muscle cells (VSMCs) and breakdown of extracellular matrix components. Angiopoietin (Ang)-1, Ang-2, interferon-␥, and VEGF-C also disrupted VSMC integrity with an Ang-2 inhibitor abrogating the effect of uNK cell CM. These results provide compelling evidence that uNK cells contribute to the early stages of spiral artery remodeling; failure of this process could contribute to pregnancy pathologynatural killer cells initiate spiral artery remodeling in human pregnancy. FASEB J.
Journal of leukocyte biology, 2015
During pregnancy, a specialized type of NK cell accumulates in the lining of the uterus (decidua) and interacts with semiallogeneic fetal trophoblast cells. dNK cells are functionally and phenotypically distinct from PB NK and are implicated in regulation of trophoblast transformation of the uterine spiral arteries, which if inadequately performed, can result in pregnancy disorders. Here, we have used uterine artery Doppler RI in the first trimester of pregnancy as a proxy measure of the extent of transformation of the spiral arteries to identify pregnancies with a high RI, indicative of impaired spiral artery remodeling. We have used flow cytometry to examine dNK cells isolated from these pregnancies compared with those from pregnancies with a normal RI. We report a reduction in the proportion of dNK cells from high RI pregnancies expressing KIR2DL/S1,3,5 and LILRB1, receptors for HLA-C and HLA-G on trophoblast. Decreased LILRB1 expression in the decidua was examined by receptor bl...
Human uterine natural killer cells: a reappraisal
Molecular immunology, 2005
The presence of granulated cells within the uterus of many species has been recognised for many years but only recently have these been recognised to be a type of NK cell. Various terms have been applied to the cells, including endometrial granulocyte, K cell and, in mouse and rat, granulated metrial gland cell. Although early studies are often based on histology and electron microscopy, these often include important information for current studies. In vitro studies of purified cells have focused particularly on cytotoxicity and cytokine production and roles in the control of trophoblast invasion and spiral artery remodelling in human pregnancy have been proposed. Evidence in mouse has implicated uNK cell production of IFN-gamma in vascular remodelling but evidence for such a role for human uNK cells remains to be established. Investigation of uNK cells in human pregnancy is hampered by the lack of availability of tissues from the first half of the second trimester of pregnancy when...
A Review of Trafficking and Activation of Uterine Natural Killer Cells
American Journal of Reproductive Immunology, 2005
PROBLEM-Enrichment of uterine Natural Killer (uNK) cells occurs during pregnancy in many species. However, functions of uNK cells and regulation of their uterine homing are not fully defined. In mice and women, uNK cells contribute to angiogenesis, a role reviewed here and now addressed in a mammal with an alternative placental type.
Leukocyte driven-decidual angiogenesis in early pregnancy
Cellular & Molecular Immunology, 2014
Successful pregnancy and long-term, post-natal maternal and offspring cardiac, vascular and metabolic health require key maternal cardiovascular adaptations over gestation. Within the pregnant decidualizing uterus, coordinated vascular, immunological and stromal cell changes occur. Considerable attention has been given to the roles of uterine natural killer (uNK) cells in initiating decidual spiral arterial remodeling, a process normally completed by mid-gestation in mice and in humans. However, leukocyte roles in much earlier, region specific, decidual vascular remodeling are now being defined. Interest in immune cell-promoted vascular remodeling is driven by vascular aberrations that are reported in human gestational complications such as infertility, recurrent spontaneous abortion, preeclampsia (PE) and fetal growth restriction. Appropriate maternal cardiovascular responses during pregnancy protect mothers and their children from later cardiovascular disease risk elevation. One of the earliest uterine responses to pregnancy in species with hemochorial placentation is stromal cell decidualization, which creates unique niches for angiogenesis and leukocyte recruitment. In early decidua basalis, the aspect of the implantation site that will cradle the developing placenta and provide the major blood vessels to support mature placental functions, leukocytes are greatly enriched and display specialized properties. UNK cells, the most abundant leukocyte subset in early decidua basalis, have angiogenic abilities and are essential for normal early decidual angiogenesis. The regulation of uNK cells and their roles in determining maternal and progeny cardiovascular health over pregnancy and postpartum are discussed.