Evidence map›Paper›PMID 24954223›Full record

ArticleCellular & molecular immunology2014

Ly49 receptors activate angiogenic mouse DBA⁺ uterine natural killer cells.

Patricia D A Lima, Megan M Tu, Mir Munir A Rahim, Annie R Peng, B Anne Croy, Andrew P Makrigiannis

Abstract read
In one paragraph

Article in Cellular & molecular immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Article
  2. Mesenchymal stem cells for recurrent miscarriage.Journal of translational medicine · 2026
    Review
  3. T-bet Fate Mapping Reveals Gestational Stage-Specific Transcriptional Adaptation of Decidual NK Cells.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Article
  4. Article
  5. Article
  6. Uterine Deletion ofInternational journal of molecular sciences · 2022
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Leukocyte driven-decidual angiogenesis in early pregnancy.Cellular & molecular immunology · 2014
    Review
  16. Article
  17. Article
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Patricia D A Lima1] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1N 6N5, Canada [2] Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.
Megan M TuDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
Mir Munir A RahimDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
Annie R Peng1] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1N 6N5, Canada [2] Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.
B Anne CroyBiomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.
Andrew P MakrigiannisDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.

Funding

Canadian Institutes of Health Research MOP 62841Canadian Institutes of Health Research MOP 77519
6 · The paper itself

Abstract

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 (TCRβ(-)CD122(+)DBA(+)DX5(-) (DBA(+)DX5(-))) and TCRβ(-)CD122(+)DBA(-)DX5(+) (DBA(-)DX5(+))) frequencies in pregnant uterus were similar between genotypes. Ly49(KD) lowered the normal frequencies of Ly49(+) uNK cells from 90.3% to 47.8% in DBA(-)DX5(+) and 78.8% to 6.3% in DBA(+)DX5(-) 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.

Indexed as

AnimalsAnimals, NewbornEmbryo ImplantationFemaleHLA-C AntigensKiller Cells, NaturalLymphocyte ActivationMaleMiceMice, Inbred C57BLMice, KnockoutNeovascularization, PhysiologicNK Cell Lectin-Like Receptor Subfamily APregnancyRibosomal ProteinsSignal TransductionHLA-C AntigensNK Cell Lectin-Like Receptor Subfamily ARibosomal Proteinsribosomal protein S19Vascular Endothelial Growth Factor Avascular endothelial growth factor A, mouse

Identifiers

PMID24954223
PMCPMC4197209

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.