Identification of ITGA4/ITGB7 and ITGAE/ITGB7 Expressing Subsets of Decidual Dendritic-Like Cells Within Distinct Microdomains of the Pregnant Mouse Uterus (original) (raw)
Related papers
DC within the pregnant mouse uterus influence growth and functional properties of uterine NK cells
European Journal of Immunology, 2009
The vascular addressins mucosal addressin cell adhesion molecule-1, P-selectin and ICAM-1 permit a 4 b 7 -integrin-expressing DC, especially those of the myeloid lineage (CD11c 1 CD11b 1 DC), to access the pregnant mouse uterus. Injection of blocking monoclonal antibodies against mucosal addressin cell adhesion molecule-1 in P-selectin À/À mice or experimental approaches with b7-integrin À/À or ICAM-1 À/À mice revealed that limited access or absence of CD11c 1 CD11b 1 DC at the maternal/fetal interface negatively affects the frequency, size and functional properties of uterine NK (uNK) cells. Adoptive transfer of DC obtained from WT mice into b7-integrin À/À mice abrogates these effects and emphasizes the importance of DC in uNK cell differentiation. Interestingly, those implantation sites lacking CD11c 1 CD11b 1 DC are characterized by decreased IL-15 and IL-12 mRNA and/or protein levels. Chronic administration of IL-15 in these mice gives rise to uNK cell numbers and size comparable to those of WT mice, whereas additional injection of IL-12 positively affects the IFN-c expression of uNK cells. Real-time RT-PCR and protein arrays performed with isolated uterine DC underline the role of DC as a source of IL-15 and IL-12 in the pregnant mouse uterus.
Decidual NK cells regulate key developmental processes at the human fetal-maternal interface
Nature Medicine, 2006
Human CD56 bright NK cells accumulate in the maternal decidua during pregnancy and are found in direct contact with fetal trophoblasts. Several mechanisms have been proposed to explain the inability of NK cells to kill the semiallogeneic fetal cells. However, the actual functions of decidual NK (dNK) cells during pregnancy are mostly unknown. Here we show that dNK cells, but not peripheral blood-derived NK subsets, regulate trophoblast invasion both in vitro and in vivo by production of the interleukin-8 and interferon-inducible protein-10 chemokines. Furthermore, dNK cells are potent secretors of an array of angiogenic factors and induce vascular growth in the decidua. Notably, such functions are regulated by specific interactions between dNK-activating and dNK-inhibitory receptors and their ligands, uniquely expressed at the fetal-maternal interface. The overall results support a 'peaceful' model for reproductive immunology, in which elements of innate immunity have been incorporated in a constructive manner to support reproductive tissue development.
Immunological Investigations, 2005
Natural Killer (NK) lymphocytes, strongly expressing CD56, become abundant in the human uterus three to five days after the mid-menstrual cycle surge in pituitary-derived luteinizing hormone (LH). The primary functions of LH are to initiate final oocyte maturation/ovulation and to contribute to decidualization of the uterine stroma. Decidualization is the transformation of estrogen-primed uterine stromal fibroblasts into large hormone producing cells under the influence of progesterone (P 4). Decidual CD56 bright (dNK) cells are a distinct, transient, tissue-specific NK cell subset that undergoes proliferation, terminal differentiation, and then death prior to menses. If pregnancy occurs, dNK cells increase during first trimester, then decline and are virtually absent in late pregnancy. In mouse models, pregnancy-associated uterine NK (uNK) cells appear coincident with onset of decidualization during embryonic implantation. Murine uNK cells traffic from the circulation to the anti-mesometrial side of the uterus and migrate to the mesometrial side of each implantation site. Here they proliferate and are implicated in regulation of mid-gestation structural changes to major arteries supplying the placenta, before dying in late gestation. Emerging data indicate that interactions between lymphocytes and endothelial cells within the uterine microenvironment are mediated by classical molecules associated with lymphocyte trafficking in immune surveillance and in response to inflammation. Here, we review factors influencing NK cell trafficking to decidualizing murine and human uteri and the differentiation and functions of these cells within the uterus.
Induced Human Decidual NK-Like Cells Improve Utero-Placental Perfusion in Mice
PLOS ONE, 2016
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. Here, gene expression profiling shows that CD56 Bright idNK cells derived ex vivo from human pNK cells, and to a lesser extent CD56 Dim idNK cells, are enriched in the gene expression signature that distinguishes dNK cells from pNK cells. When injected into immunocompromised pregnant mice with elevated uterine artery resistance, idNK cells homed to the uterus and reduced the uterine artery resistance index, suggesting improved placental perfusion.
Immune cells in the placental bed
The International Journal of Developmental Biology, 2010
Leukocytes are an important component of the human uterine decidua in normal pregnancy. The focus of research has been on the more abundant populations such as the uterine natural killer (uNK) cells and macrophages, but more recently interest has also extended to less abundant, but functionally significant populations. Investigation of function in human pregnancy is limited by the scope of in vitro studies and the inability to perform in vivo manipulation of cell populations. Investigation of pathological pregnancy may provide clues to function, although acquisition of samples is limited until after clinical presentation. Investigation of animal models may provide clues to function in humans and this has certainly been the case for the uNK cells. However, human placentation differs substantially from the usual laboratory animal models and any extrapolation to humans from animal studies should be made with this in mind. Considerable advances have been made over the last 25 years but many questions still remain; the next 25 years may provide more answers to the role of the endometrial leukocytes in normal pregnancy, so that further advances can be made in investigation of their role, if any, in pregnancy pathology.
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 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 ...
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...