ArticleScientific reports2015
Tim-3 protects decidual stromal cells from toll-like receptor-mediated apoptosis and inflammatory reactions and promotes Th2 bias at the maternal-fetal interface.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 69 citations in OpenAlex.
- Unraveling the Role of Azobenzene-Based Photoswitchable Lipids in Controlling Innate Immune Response.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Anti-atherogenic immune checkpoint TIM-3 as a promising pharmacologic target toward ischemic heart diseases: a prospective review.Molecular biology reports · 2025Review
- Review
- Involvement of Tim-3 in Maternal-fetal Tolerance: A Review of Current Understanding.International journal of biological sciences · 2025Review
- 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
- The regulated cell death at the maternal-fetal interface: beneficial or detrimental?Cell death discovery · 2024Review
- TIM proteins and microRNAs: distinct impact and promising interactions on transplantation immunity.Frontiers in immunology · 2024Review
- Paradoxical expression of NRP1 in decidual stromal and immune cells reveals a novel inflammation balancing mechanism during early pregnancy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Estrogen-sensitive activation of SGK1 induces M2 macrophages with anti-inflammatory properties and a Th2 response at the maternal-fetal interface.Reproductive biology and endocrinology : RB&E · 2023Article
- Minding the Bathwater: Fertility and Reproductive Toxicity in the Age of Immuno-Oncology.JCO oncology practice · 2022Review
- The Role of the Immune Checkpoint Molecules PD-1/PD-L1 and TIM-3/Gal-9 in the Pathogenesis of Preeclampsia-A Narrative Review.Medicina (Kaunas, Lithuania) · 2022Review
- Immunological Changes in Pregnancy and Prospects of Therapeutic Pla-Xosomes in Adverse Pregnancy Outcomes.Frontiers in pharmacology · 2022Review
- Involvement of the Tim-3 Pathway in the Pathogenesis of Pre-Eclampsia.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
- Regulation of the innate immune cells during pregnancy: An immune checkpoint perspective.Journal of cellular and molecular medicine · 2021Review
- Differences in Immune Checkpoints Expression (TIM-3 and PD-1) on T Cells in Women with Recurrent Miscarriages-Preliminary Studies.Journal of clinical medicine · 2021Article
- Uterine Notch2 facilitates pregnancy recognition and corpus luteum maintenance via upregulating decidual Prl8a2.PLoS genetics · 2021Article
- Soluble TIM3 and Its Ligands Galectin-9 and CEACAM1 Are in Disequilibrium During Alcohol-Related Liver Disease and Promote Impairment of Anti-bacterial Immunity.Frontiers in physiology · 2021Article
- Effects of aspirin, vitamin D3, and progesterone on pregnancy outcomes in an autoimmune recurrent spontaneous abortion model.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2021Article
- Placental Immune Tolerance and Organ Transplantation: Underlying Interconnections and Clinical Implications.Frontiers in immunology · 2021Review
- Glial TIM-3 Modulates Immune Responses in the Brain Tumor Microenvironment.Cancer research · 2020Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptors (TLRs) are important in mediating immune responses against various pathogens during pregnancy. However, uncontrolled TLR-triggered inflammation will endanger normal pregnancy, resulting in pregnancy loss. Therefore, maintenance of a moderate inflammatory response is crucial for successful pregnancy under conditions of infection. Here, we demonstrated significantly lowered expression of T-cell immunoglobulin and mucin domain 3 (Tim-3) in miscarried decidual stromal cells (DSCs), indicating that Tim-3 might play important roles in maintaining successful pregnancies. Activation of TLR signaling induced pro-inflammatory cytokine production and apoptosis of DSCs, which was accompanied by up-regulated Tim-3 expression. Tim-3, in turn, protected DSCs from TLR-mediated apoptosis in an ERK1/2 pathway-dependent manner. In addition, Tim-3 inhibited TLR signaling-induced inflammatory cytokine production by DSCs through suppressing NF-κB activation. Tim-3 increased production of T helper 2 (Th2)-type cytokines by DSCs and reversed the inhibitory effect of LPS on Th2 cytokine generation by up-regulation of interferon regulatory factor 4 expression. Tim-3 blockade abolished the effect of Tim-3 on the inflammatory response to LPS stimulation. Thus, Tim-3 signaling could represent a "self-control" mechanism in TLR-triggered inflammation during pregnancy. These findings identify Tim-3 as a key regulator of DSCs and suggest its potential as a target for the treatment of spontaneous abortion.
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