ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Activating KIR2DS4 Is Expressed by Uterine NK Cells and Contributes to Successful Pregnancy.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 3 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 3 syntheses or guidelines pooled it, 97 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
- The CD94/NKG2A inhibitory receptor educates uterine NK cells to optimize pregnancy outcomes in humans and mice.Immunity · 2021Pooled it
- Crosstalk Between Trophoblasts and Decidual Immune Cells: The Cornerstone of Maternal-Fetal Immunotolerance.Frontiers in immunology · 2021Pooled 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
- Examining the association between fetal HLA-C, maternal KIR haplotypes and birth weight.PLoS genetics · 2026Article
- 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
- The role of dysbiosis in shaping host immunity in endometrial cancer development.Frontiers in immunology · 2025Review
- Peptide-specific natural killer cell receptors.Oxford open immunology · 2025Review
- Immune modulation permits tolerance and engraftment in a murine model of late-gestation transplantation.Blood advances · 2024Article
- Is the Complement System Dysregulated in Preeclampsia Comorbid with HIV Infection?International journal of molecular sciences · 2024Review
- Human CD56National science review · 2024Article
- The chemokine XCL1 functions as a pregnancy hormone to program offspring innate anxiety.Brain, behavior, and immunity · 2024Article
- Exploring HLA-C methylation patterns and nutritional status in Kichwa mothers and infants from Tena, Ecuador.Frontiers in medicine · 2024Article
- Endometrial TGFβ signaling fosters early pregnancy development by remodeling the fetomaternal interface.American journal of reproductive immunology (New York, N.Y. : 1989) · 2023Review
- IL-21R-STAT3 signalling initiates a differentiation program in uterine tissue-resident NK cells to support pregnancy.Nature communications · 2023Article
- Immune Dysfunction in Polycystic Ovary Syndrome.ImmunoHorizons · 2023Review
- Local immune recognition of trophoblast in early human pregnancy: controversies and questions.Nature reviews. Immunology · 2023Review
- The central role of natural killer cells in preeclampsia.Frontiers in immunology · 2023Review
- Immunogenomics of Killer Cell Immunoglobulin-Like Receptor (KIR) and HLA Class I: Coevolution and Consequences for Human Health.The journal of allergy and clinical immunology. In practice · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Tissue-specific NK cells are abundant in the pregnant uterus and interact with invading placental trophoblast cells that transform the maternal arteries to increase the fetoplacental blood supply. Genetic case-control studies have implicated killer cell Ig-like receptor (KIR) genes and their HLA ligands in pregnancy disorders characterized by failure of trophoblast arterial transformation. Activating KIR2DS1 or KIR2DS5 (when located in the centromeric region as in Africans) lower the risk of disorders when there is a fetal HLA-C allele carrying a C2 epitope. In this study, we investigated another activating KIR, KIR2DS4, and provide genetic evidence for a similar effect when carried with KIR2DS1 KIR2DS4 is expressed by ∼45% of uterine NK (uNK) cells. Similarly to KIR2DS1, triggering of KIR2DS4 on uNK cells led to secretion of GM-CSF and other chemokines, known to promote placental trophoblast invasion. Additionally, XCL1 and CCL1, identified in a screen of 120 different cytokines, were consistently secreted upon activation of KIR2DS4 on uNK cells. Inhibitory KIR2DL5A, carried in linkage disequilibrium with KIR2DS1, is expressed by peripheral blood NK cells but not by uNK cells, highlighting the unique phenotype of uNK cells compared with peripheral blood NK cells. That KIR2DS4, KIR2DS1, and some alleles of KIR2DS5 contribute to successful pregnancy suggests that activation of uNK cells by KIR binding to HLA-C is a generic mechanism promoting trophoblast invasion into the decidua.
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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.