Differential transcription of Eomes and T-bet during maturation of mouse uterine natural killer cells

Tayade, Chandrakant; Yuan, Fang; Black, Gordon P.; Va, Paffaro; Erlebacher, Adrian; Croy, B. Anne

doi:10.1189/jlb.0305142

Cited by 60 publications

(52 citation statements)

References 40 publications

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“…30 These data indicate that IFNG expression is not Ly49 receptordependent, but is dependent upon NKG2D, 36 a functional receptor in B6.Ly49 KD mice. 30 Since some studies suggest that uNK cells use a different transcription factor for IFNG regulation than peripheral NK cells, 37 alternative explanations for normal levels of IFNG in B6.Ly49 KD decidua basalis must also be considered. For example, DBA 2 DX5 1 uNK cells that are responsible for most to all of the IFNG production in early decidua were much less severely affected by the Ly49 KD than the angiogenic DBA 1 uNK cells.…”

Section: Discussionmentioning

confidence: 99%

Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells

Lima

Rahim

et al. 2014

Cell Mol Immunol

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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.

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Section: Discussionmentioning

confidence: 99%

Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells

Lima

Rahim

et al. 2014

Cell Mol Immunol

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“…15 The use of DBA lectin was widely adopted because it is more visually distinct than PAS in histological sections and is compatible with RNA isolation after cell collection from tissues by laser capture microdissection while PAS is not. 16 Additionally, DBA lectin can be magnetically tagged for isolation of uNK cells from decidual cell suspensions for fluorescence-activated cell sorting, short-term culture or RNA isolation. 16 We asked if PAS and DBA lectin were fully coincident stains and documented that they were not.…”

Section: Dbamentioning

confidence: 99%

Natural killer cell-triggered vascular transformation: maternal care before birth?

et al. 2010

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Natural killer (NK) cells are found in lymphoid and non-lymphoid organs. In addition to important roles in immune surveillance, some NK cells contribute to angiogenesis and circulatory regulation. The uterus of early pregnancy is a non-lymphoid organ enriched in NK cells that are specifically recruited to placental attachment sites. In species with invasive hemochorial placentation, these uterine natural killer (uNK) cells, via secretion of cytokines, chemokines, mucins, enzymes and angiogenic growth factors, contribute to the physiological change of mesometrial endometrium into the unique stromal environment called decidua basalis. In humans, uNK cells have the phenotype CD56 bright CD16 dim and they appear in great abundance in the late secretory phase of the menstrual cycle and early pregnancy. Gene expression studies indicate that CD56 bright CD16 dim uterine and circulating cells are functionally distinct. In humans but not mice or other species with post-implantation decidualization, uNK cells may contribute to blastocyst implantation and are of interest as therapeutic targets in female infertility. Histological and genetic studies in mice first identified triggering of the process of gestation spiral arterial modification as a major uNK cell function, achieved via interferon (IFN)-c secretion. During spiral arterial modification, branches from the uterine artery that traverse the endometrium/decidua transiently lose their muscular coat and ability to vasoconstrict. The expression of vascular markers changes from arterial to venous as these vessels dilate and become low-resistance, high-volume channels. Full understanding of the vascular interactions of human uNK cells is difficult to obtain because endometrial time-course studies are not possible in pregnant women. Here we briefly review key information concerning uNK cell functions from studies in rodents, summarize highlights concerning human uNK cells and describe our preliminary studies on development of a humanized, pregnant mouse model for in vivo investigations of human uNK cell functions.

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“…Both of these parameters normally increase as uNK cells mature (21). Approximately 200 -300 morphologically homogeneous uNK cells of each of four distinct subtypes were collected by focal laser melting of the thermoplastic film from the cap onto the individual desired cells using multiple implantation sites for cell harvesting (24). The four uNK cell subtypes used were as follows: 1) agranular (AG; DBA ϩ , Ͻ9-m diameter); 2) immature (IM; DBA ϩ , ϳ13-m diameter, Ͻ5 cytoplasmic granules); 3) granular (DBA ϩ , 20-to 30-m diameter, heavily granulated Ͻ10 cytoplasmic granules); or 4) senescent (DBA ϩ , Ͼ30-m diameter, apoptotic nuclei, vacuolated cytoplasm, irregular rather than rounded shape Ͼ10 cytoplasmic granules).…”

Section: Lcm Of Unk Cells Rna Isolation and Cdna Synthesismentioning

confidence: 99%

“…Cryostat sections were cut at 7 m, placed on glass slides (Fisher Scientific), and either stored at Ϫ80°C for subsequent use or stained immediately using a rapid Dolichos biflorus agglutinin (DBA) lectin-staining protocol to identify uNK cells as described previously (24). DBA lectin staining produces a distinct brown coloration over the surface of all uNK cells and over the membranes encapsulating uNK cell cytoplasmic granules once granules begin to develop.…”

Section: Lcm Of Unk Cells Rna Isolation and Cdna Synthesismentioning

confidence: 99%

Genetic Deletion of Placenta Growth Factor in Mice Alters Uterine NK Cells

Tayade

Hilchie

et al. 2007

The Journal of Immunology

110

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Placenta growth factor (PlGF; formerly PGF), a vascular endothelial growth factor gene family member, is expressed in human implantation sites by maternal uterine NK (uNK) and fetal trophoblast cells. Lower than normal concentrations of blood and urinary PlGF have been associated with impending onset of pre-eclampsia, a hypertensive disease of late human gestation characterized by limited intravascular trophoblast invasion. In pregnant rodents, delivery of the PlGF antagonist sFlt-1 or S-endoglin induces pre-eclampsia-like lesions. Mice genetically deleted in PlGF reproduce, but neither their implantation sites nor their uNK cell development are described. We combined real-time PCR of endometrium from nonpregnant and gestation day (gd)6–18 C57BL6/J (B6) mice with immunohistology to analyze PlGF expression in normal mouse pregnancy. To estimate the significance of uNK cell-derived PlGF, PlGF message was quantified in mesometrial decidua from pregnant alymphoid Rag2 null/common γ chain null mice and in laser capture-microdissected B6 uNK cells. Histopathologic consequences from PlGF deletion were also characterized in the implantation sites from PlGF null mice. In B6, decidual PlGF expression rose between gd8–16. uNK cells were among several types of cells transcribing PlGF in decidualized endometrium. Immature uNK cells, defined by their low numbers of cytoplasmic granules, were the uNK cells displaying the greatest number of transcripts. PlGF deletion promoted the early differentiation high numbers of binucleate uNK cells (gd8) but had no other significant, morphometrically detectable impact on implantation sites. Thus, in mice, PlGF plays an important role in successful uNK cell proliferation and/or differentiation.

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Differential transcription of Eomes and T-bet during maturation of mouse uterine natural killer cells

Cited by 60 publications

References 40 publications

Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells

Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells

Natural killer cell-triggered vascular transformation: maternal care before birth?

Genetic Deletion of Placenta Growth Factor in Mice Alters Uterine NK Cells

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