Perforin-expressing granulated metrial gland cells in murine deciduoma.

Zheng, Lan; Joag, Sanjay V.; Parr, Margaret B.; Parr, Earl L.; Young, John Ding‐E

doi:10.1084/jem.174.5.1221

Cited by 26 publications

(16 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is noteworthy to mention here that uNK cells are present in decidualized pseudopregnant rats or mice. They are probably phenotypically distinct from uNK cells accumulating in a pregnant uterus (Peel et al , 1979; Stewart 1988; Zheng et al , 1991). Two observations suggest that trophoblasts may not be a prerequisite for uNK cell amplification.…”

Section: Uterine Nk Cells and Tregs In Pregnancy: Why Are They There mentioning

confidence: 99%

Natural killer cells and regulatory T cells in early pregnancy loss

Sharma¹

2014

Int. J. Dev. Biol.

125

107

View full text Add to dashboard Cite

Survival of the allogeneic embryo in the uterus depends on the maintenance of immune tolerance at the maternal-fetal interface. The pregnant uterus is replete with activated maternal immune cells. How this immune tolerance is acquired and maintained has been a topic of intense investigation. The key immune cells that predominantly populate the pregnant uterus are natural killer (NK) cells. In normal pregnancy, these cells are not killers, but rather provide a microenvironment that is pregnancy compatible and supports healthy placentation. In placental mammals, an array of highly orchestrated immune elements to support successful pregnancy outcome has been incorporated. This includes active cooperation between maternal immune cells, particularly NK cells, and trophoblast cells. This intricate process is required for placentation, immune regulation and to remodel the blood supply to the fetus. During the past decade, various types of maternal immune cells have been thought to be involved in cross-talk with trophoblasts and in programming immune tolerance. RegulatoryT cells (Tregs) have attracted a great deal of attention in promoting implantation and immune tolerance beyond implantation. However, what has not been fully addressed is how this immune-trophoblast axis breaks down during adverse pregnancy outcomes, particularly early pregnancy loss, and in response to unscheduled inflammation. Intense research efforts have begun to shed light on the roles of NK cells and Tregs in early pregnancy loss, although much remains to be unraveled in order to fully characterize the mechanisms underlying their detrimental activity. An increased understanding of host-environment interactions that lead to the cytotoxic phenotype of these otherwise pregnancy compatible maternal immune cells is important for prediction, prevention and treatment of pregnancy maladies, particularly recurrent pregnancy loss. In this review, we discuss relevant information from experimental and human models that may explain the pregnancy disrupting roles of these pivotal sentinel cells at the maternal-fetal interface.

show abstract

Section: Uterine Nk Cells and Tregs In Pregnancy: Why Are They There mentioning

confidence: 99%

Natural killer cells and regulatory T cells in early pregnancy loss

Sharma¹

2014

Int. J. Dev. Biol.

125

107

View full text Add to dashboard Cite

show abstract

“…16,17 Although mouse trophoblast cells express MHC molecules, 18 mouse uNK cells may have only an indirect influence on trophoblast invasion. 14 UNK cells in both humans and mice synthesize cytoplasmic granules that contain perforin and granzymes; [19][20][21] however, uNK cells are generally regarded as displaying limited lytic activity. Mouse, but not human, uNK cells bind Dolichos biflorus agglutinin (DBA) lectin 17,22 to membranes of the cell and of their numerous cytoplasmic granules.…”

Section: Introductionmentioning

confidence: 99%

Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells

Lima

Rahim

et al. 2014

Cell Mol Immunol

View full text Add to dashboard Cite

In humans, specific patterns of killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer (uNK) cells are linked through HLA-C with pregnancy complications (infertility, recurrent spontaneous abortion, intrauterine growth restriction and preeclampsia). To identify mechanisms underpinning the associations between NK cell activation and pregnancy success, pregnancies were studied in mice with genetic knockdown (KD) of the MHC-activated Ly49 receptor gene family. B6.Ly49 KD pregnancies were compared to normal control B6.Ly49 129 and C57BL/6 (B6) pregnancies. At mid-pregnancy (gestation day (gd9.5)), overall uNK cell (TCRb 2 CD122 1 DBA 1 DX5 2 (DBA 1 DX5 2 )) and TCRb 2 CD122 1 DBA 2 DX5 1 (DBA 2 DX5 1 )) frequencies in pregnant uterus were similar between genotypes. Ly49 KD lowered the normal frequencies of Ly49 1 uNK cells from 90.3% to 47.8% in DBA 2 DX5 1 and 78.8% to 6.3% in DBA 1 DX5 2 uNK cell subtypes. B6.Ly49 KD matings frequently resulted in expanded blastocysts that did not implant (subfertility). B6.Ly49 KD mice that established pregnancy had gestational lengths and litter sizes similar to controls. B6.Ly49 KD neonates, however, were heavier than controls. B6.Ly49 KD implantation sites lagged in early (gd6.5) decidual angiogenesis and were deficient in mid-pregnancy (gd10.5) spiral arterial remodelling. Ultrastructural analyses revealed that B6.Ly49 KD uNK cells had impaired granulogenesis, while immunocytochemistry revealed deficient vascular endothelial cell growth factor (VEGFA) production. Perforin and IFNG expression were normal in B6.Ly49 KD uNK cells. Thus, in normal mouse pregnancies, Ly49 receptor signaling must promote implantation, early decidual angiogenesis and mid-pregnancy vascular remodelling. Disturbances in these functions may underlie the reported genetic associations between human pregnancy complications and the inability of specific conceptus MHCs to engage activating KIR on uNK cells.

show abstract

“…They are easily distinguished from other stromal cells by large periodic-acid-Schiff-reagent (PAS)-stained glycoprotein granules situated at one aspect of the nucleus (Stewart and Peel 1980). These granules also contain perforin (Zheng et al 1991) and serine proteases (Parr et al 1990). Furthermore, GMG cells express asialo GM1, NK1.1, interleukin-2 (IL-2) receptor-beta (Mukhtar et al 1989), and NKR-P1 (Head et al 1994), but are negative for CD3.…”

Section: Introductionmentioning

confidence: 97%

Expression of vascular endothelial growth factor by granulated metrial gland cells in pregnant murine uteri

Wang

Umesaki

Nakamura

et al. 2000

Cell and Tissue Research

View full text Add to dashboard Cite

Granulated metrial gland (GMG) cells are a characteristic uterine component belonging to a natural killer cell lineage. This study is aimed at revealing their kinetic and spatial relationship with vascular growth during pregnancy and the expression of vascular endothelial growth factor (VEGF). GMG cells and blood vessels were identified by periodic-acid-Schiff-reagent (PAS)-stained granules and positive staining for factor-VIII-related antigen, respectively. GMG cells were widely distributed in the decidua and metrial gland and showed a numerical increase with a peak at day 13 in parallel with the increase of vascular density. Preceding the maximal vascular development at day 13, microvessels with a narrow lumen representative of neovascularization prevailed at days 7-9, and the VEGF content in the decidua/metrial gland was significantly elevated at days 7-13 concurrently with mRNA expression. By immunolight microscopy combined with PAS staining, GMG cells with PAS-stained granules were positive for VEGF. Immunoelectron microscopy demonstrated that immunoreactions were diffuse in the cytoplasm but not localized in the granules. In contrast, fibroblast-like stromal cells were negative. These data indicate that GMG cells express VEGF and may play inducing roles in uterine neovascularization during pregnancy.

show abstract

Perforin-expressing granulated metrial gland cells in murine deciduoma.

Cited by 26 publications

References 12 publications

Natural killer cells and regulatory T cells in early pregnancy loss

Natural killer cells and regulatory T cells in early pregnancy loss

Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells

Expression of vascular endothelial growth factor by granulated metrial gland cells in pregnant murine uteri

Contact Info

Product

Resources

About