ArticleCellular & molecular immunology2016
The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at the maternal-fetal interface in early pregnancy.
Article in Cellular & molecular immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- Crosstalk Between Trophoblasts and Decidual Immune Cells: The Cornerstone of Maternal-Fetal Immunotolerance.Frontiers in immunology · 2021Pooled it
- Trial
- Unconventional functions of natural killer cells in homeostasis and disease.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Engineered Mesenchymal Stem Cell-NK Cell Complexes for Spatially Targeted and Functionally Revitalized Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Peripheral Regulatory T Cells Display Dynamic Memory Subset Frequency and Inhibitory Marker Expression Across Pregnancy.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Article
- Sex Hormones-Mediated Modulation of Immune Checkpoints in Pregnancy and Recurrent Pregnancy Loss.International journal of molecular sciences · 2026Article
- Immune checkpoint TIM-3 in tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Inhibitory immune checkpoints in preeclampsia: current landscape, mechanisms, and clinical perspectives.Frontiers in immunology · 2026Review
- Microfluidic chip-integrated vascularized endometrial complexes: Mitochondrial function and paracrine crosstalk enhance regenerative potential.Bioactive materials · 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
- The Sweet Side of IVF: Biological Role and Diagnostic Potential of Galectin-9 in Female Infertility.International journal of molecular sciences · 2025Article
- Role of galectin-9 in the development of gestational diabetes mellitus.Scientific reports · 2025Article
- Immune checkpoint for pregnancy.Seminars in immunopathology · 2025Review
- Endometrial Stromal Senescence Mediates the Progression of Intrauterine Adhesions.International journal of molecular sciences · 2025Article
- Differential impact of TIM-3 ligands on NK cell function.Journal for immunotherapy of cancer · 2025Article
- Involvement of Tim-3 in Maternal-fetal Tolerance: A Review of Current Understanding.International journal of biological sciences · 2025Review
- Surface Immune Checkpoints as Potential Biomarkers in Physiological Pregnancy and Recurrent Pregnancy Loss.International journal of molecular sciences · 2024Article
- MUC16 can Predict the Pregnancy Outcomes in Human and Intraperitoneal Administration of MUC16 can Rescue Pregnancy Losses in Mouse Models.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- The effect of Toxoplasma gondii infection on galectin-9 expression in decidual macrophages contributing to dysfunction of decidual NK cells during pregnancy.Parasites & vectors · 2024Article
- Effect of Cyclosporine A on Th1/Th2 Cytokine Production by Decidual Stromal Cells Mediated by Trophoblast-derived Galectin-9.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Decidual natural killer (dNK) cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immune balance between tolerance and anti-infection immune responses during pregnancy remains unknown. Here, we demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) are expressed on over 60% of dNK cells. Tim-3(+) dNK cells display higher interleukin (IL)-4 and lower tumor necrosis factor (TNF)-α and perforin production. Human trophoblast cells can induce the transformation of peripheral NK cells into a dNK-like phenotype via the secretion of galectin-9 (Gal-9) and the interaction between Gal-9 and Tim-3. In addition, trophoblasts inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokine and perforin production by dNK cells, which can be attenuated by Tim-3 neutralizing antibodies. Interestingly, a decreased percentage of Tim-3-expressing dNK cells were observed in human miscarriages and murine abortion-prone models. Moreover, T helper (Th)2-type cytokines were decreased and Th1-type cytokines were increased in Tim-3(+) but not Tim-3(-) dNK cells from human and mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is important for the regulation of dNK cell function, which is beneficial for the maintenance of a normal pregnancy.
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