ArticleThe Journal of clinical investigation2013
Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 4 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
149 citing papers in PubMed, 4 syntheses or guidelines pooled it, 265 citations in OpenAlex.
- Number and function of uterine natural killer cells in recurrent miscarriage and implantation failure: a systematic review and meta-analysis.Human reproduction update · 2022Pooled it
- Crosstalk Between Trophoblasts and Decidual Immune Cells: The Cornerstone of Maternal-Fetal Immunotolerance.Frontiers in immunology · 2021Pooled it
- Recurrent Spontaneous Abortion (RSA) and Maternal KIR Genes: A Comprehensive Meta-Analysis.JBRA assisted reproduction · 2020Pooled it
- The Roles of Uterine Natural Killer (NK) Cells and KIR/HLA-C Combination in the Development of Preeclampsia: A Systematic Review.BioMed research international · 2020Pooled it
- Gene regulation at the early human maternal-fetal interface.Nature reviews. Genetics · 2026Review
- Deciphering the maternal uterine signals that shape placenta development.Reproduction (Cambridge, England) · 2026Review
- Protein language models accurately predict polymorphic peptide-modulated NK cell receptor-HLA class I interaction strengths.Science advances · 2026Article
- Examining the association between fetal HLA-C, maternal KIR haplotypes and birth weight.PLoS genetics · 2026Article
- Decidual immune activation by extravillous trophoblasts drives maternal-fetal tolerance and immunity.Trends in immunology · 2026Article
- T-bet Fate Mapping Reveals Gestational Stage-Specific Transcriptional Adaptation of Decidual NK Cells.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Article
- Dipeptidylpeptidase 4 inhibition attenuates gestational pathologies via immune homeostasis restoration in the pulmonary-uterine axis.Nature communications · 2026Article
- Integrative Roles of NK Receptors and γδ TCRs in γδ T Cell-Mediated Cancer Immunity.Immune network · 2026Review
- Partial embryo loss caused by disruption of the placental hormone CTRP6 coincides with dNK cell abnormalities during pregnancy.iScience · 2026Article
- A rare variant in theArchives of medical science : AMS · 2026Article
- TGFBR2 coordinates the endometrial response to estrogen, regulating endometrial hyperplasia and fertility.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Investigating the functional capacity of porcine uterine natural killer cells during a porcine reproductive and respiratory syndrome virus infection of pregnant gilts.Veterinary research · 2025Article
- Cytokine and metabolite networks shape T cell residency and functionality at the term human maternal-fetal interface.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Dual Role of Natural Killer Cells in Early Pregnancy: Immunopathological Implications and Therapeutic Potential in Recurrent Spontaneous Abortion and Recurrent Implantation Failure.Cell proliferation · 2025Review
- Granulysin-high decidual NK cells in macaques and humans share signatures of immune defense.Cell reports · 2025Article
- Immune development differs between preterm newborns fed mothers' own milk and donor milk.iScience · 2025Article
89 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Reduced trophoblast invasion and vascular conversion in decidua are thought to be the primary defect of common pregnancy disorders including preeclampsia and fetal growth restriction. Genetic studies suggest these conditions are linked to combinations of polymorphic killer cell Ig-like receptor (KIR) genes expressed by maternal decidual NK cells (dNK) and HLA-C genes expressed by fetal trophoblast. Inhibitory KIR2DL1 and activating KIR2DS1 both bind HLA-C2, but confer increased risk or protection from pregnancy disorders, respectively. The mechanisms underlying these genetic associations with opposing outcomes are unknown. We show that KIR2DS1 is highly expressed in dNK, stimulating strong activation of KIR2DS1+ dNK. We used microarrays to identify additional responses triggered by binding of KIR2DS1 or KIR2DL1 to HLA-C2 and found different responses in dNK coexpressing KIR2DS1 with KIR2DL1 compared with dNK only expressing KIR2DL1. Activation of KIR2DS1+ dNK by HLA-C2 stimulated production of soluble products including GM-CSF, detected by intracellular FACS and ELISA. We demonstrated that GM-CSF enhanced migration of primary trophoblast and JEG-3 trophoblast cells in vitro. These findings provide a molecular mechanism explaining how recognition of HLA class I molecules on fetal trophoblast by an activating KIR on maternal dNK may be beneficial for placentation.
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Registered trials
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.