ArticleThe Journal of experimental medicine2022
EP3 enhances adhesion and cytotoxicity of NK cells toward hepatic stellate cells in a murine liver fibrosis model.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 48 citations in OpenAlex.
- Hepatic fibrosis extracellular matrix stiffness induces abnormal maturation of dendritic cell via AMPK inhibition-mediated cholesterol accumulation.Materials today. Bio · 2026Article
- GDF15 in Liver Fibrosis: Molecular Mechanisms, Immunoregulatory Functions, and Therapeutic Potential.Biomolecules · 2026Review
- Total Flavonoids fromInternational journal of molecular sciences · 2026Article
- Chronic liver diseases aggravate radiation-induced intestinal injury through taurocholic acid dysregulation.Journal of translational medicine · 2026Article
- The dual roles of natural killer cells in liver immunity and tolerance: Implications for health and disease.Hepatology communications · 2026Review
- Cofilin-1 Exacerbates Tau-Induced Mitochondrial Damage, Oxidative Stress, and Apoptosis in Alzheimer's Disease.Neurochemical research · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- CD36 aggravates ferroptosis in NK cells and dampens their anti-fibrotic activity in the liver.Frontiers in immunology · 2026Article
- Spatial niche remodeling of senescent liver-resident immune cells and its role in chronic liver diseases.Frontiers in medicine · 2026Review
- Mendelian Randomization Reveals Genetic Associations Between Immune Traits and Urethral Stricture.Mediators of inflammation · 2026Article
- TIGIT impairs NK cell antifibrotic activity through the IFNγ-IFI30 axis in schistosomiasis-induced liver fibrosis.Frontiers in immunology · 2026Article
- Interaction between NKG2D and its ligands MICA/B activates the DAP12/SYK/p53/p21 axis to drive pulmonary fibrosis.Frontiers in immunology · 2026Article
- Integrating mechanical cues inFrontiers in immunology · 2026Review
- Deletion of EP3 prostaglandin receptor in murine macrophages aggravates diet-induced obesity by suppressing SPARC.The EMBO journal · 2025Article
- In-depth bioinformatics analysis uncovers the crosstalk genes and immune interactions among diagnostic markers linked to natural killer cells in patients with cirrhosis and sepsis.Clinical and experimental medicine · 2025Article
- The Immune Microenvironment: New Therapeutic Implications in Organ Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- The role of immune cells in cirrhosis: evidence from a two-sample Mendelian randomization study.Scientific reports · 2025Article
- Single-Cell Sequencing Reveals the Heterogeneity of Hepatic Natural Killer Cells and Identifies the Cytotoxic Natural Killer Subset in Schistosomiasis Mice.International journal of molecular sciences · 2025Article
- SOX9: a key transcriptional regulator in organ fibrosis.Frontiers in pharmacology · 2025Review
- Specific immune landscape of heatstroke distinguished from sepsis and aseptic inflammation.International journal of medical sciences · 2025Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Natural killer (NK) cells exhibit antifibrotic properties in liver fibrosis (LF) by suppressing activated hepatic stellate cell (HSC) populations. Prostaglandin E2 (PGE2) plays a dual role in innate and adaptive immunity. Here, we found that E-prostanoid 3 receptor (EP3) was markedly downregulated in NK cells from liver fibrosis mice and patients with liver cirrhosis. NK cell-specific deletion of EP3 aggravated hepatic fibrogenesis in mouse models of LF. Loss of EP3 selectively reduced the cytotoxicity of the CD27+CD11b+ double positive (DP) NK subset against activated HSCs. Mechanistically, deletion of EP3 impaired the adhesion and cytotoxicity of DP NK cells toward HSCs through modulation of Itga4-VCAM1 binding. EP3 upregulated Itga4 expression in NK cells through promoting Spic nuclear translocation via PKC-mediated phosphorylation of Spic at T191. Activation of EP3 by sulprostone alleviated CCL4-induced liver fibrosis in mice. Thus, EP3 is required for adhesion and cytotoxicity of NK cells toward HSCs and may serve as a therapeutic target for the management of LF.
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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 Socratic graph.