ArticleHepatology (Baltimore, Md.)2012
Inhibition of natural killer cells protects the liver against acute injury in the absence of glycine N-methyltransferase.
Article in Hepatology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 62 citations in OpenAlex.
- Molecular mechanisms in MASLD/MASH-related HCC.Hepatology (Baltimore, Md.) · 2025Review
- MiR-214 promotes the antitumor effect of NK cells in colorectal cancer liver metastasis through USP27X/Bim.Cytotechnology · 2024Article
- Review
- Folic Acid Ameliorates Renal Injury in Experimental Obstructive Nephropathy: Role of Glycine N-Methyltransferase.International journal of molecular sciences · 2023Article
- TNFα and IFNγ cooperate for efficient pro- to anti-inflammatory transition of macrophages during muscle regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The role of the immune system in the pathogenesis of NAFLD and potential therapeutic impacts of mesenchymal stem cell-derived extracellular vesicles.Stem cell research & therapy · 2022Review
- EP3 enhances adhesion and cytotoxicity of NK cells toward hepatic stellate cells in a murine liver fibrosis model.The Journal of experimental medicine · 2022Article
- Immune-related pathogenesis and therapeutic strategies of nonalcoholic steatohepatitis.Archives of pharmacal research · 2022Review
- Digoxin mitigates diethylnitrosamine-induced acute liver injury in mice via limiting production of inflammatory mediators.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Crucial role of T cells in NAFLD-related disease: A review and prospect.Frontiers in endocrinology · 2022Review
- The Role of Natural Killer Cells in Nonalcoholic Steatohepatitis: An Ongoing Debate.Cellular and molecular gastroenterology and hepatology · 2022Article
- Pathophysiological Mechanisms in Non-Alcoholic Fatty Liver Disease: From Drivers to Targets.Biomedicines · 2021Review
- The role of natural killer cells in liver inflammation.Seminars in immunopathology · 2021Review
- Metformin Actions on the Liver: Protection Mechanisms Emerging in Hepatocytes and Immune Cells against NASH-Related HCC.International journal of molecular sciences · 2021Review
- Hepatoprotective Effect of Mixture of Dipropyl Polysulfides in Concanavalin A-Induced Hepatitis.Nutrients · 2021Article
- Role of Methylation in Pro- and Anti-Cancer Immunity.Cancers · 2021Review
- Corilagin Ameliorates Con A-Induced Hepatic Injury by Restricting M1 Macrophage Polarization.Frontiers in immunology · 2021Article
- Natural Killer T Cells in Various Mouse Models of Hepatitis.BioMed research international · 2021Review
- Bile Acid Toxicity and Protein Kinases.Advances in experimental medicine and biology · 2021Article
- Revisiting the Role of Natural Killer Cells in Non-Alcoholic Fatty Liver Disease.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
unlabelledGlycine N-methyltransferase (GNMT) catabolizes S-adenosylmethionine (SAMe), the main methyl donor of the body. Patients with cirrhosis show attenuated GNMT expression, which is absent in hepatocellular carcinoma (HCC) samples. GNMT(-/-) mice develop spontaneous steatosis that progresses to steatohepatitis, cirrhosis, and HCC. The liver is highly enriched with innate immune cells and plays a key role in the body's host defense and in the regulation of inflammation. Chronic inflammation is the major hallmark of nonalcoholic steatohepatitis (NASH) progression. The aim of our study was to uncover the molecular mechanisms leading to liver chronic inflammation in the absence of GNMT, focusing on the implication of natural killer (NK) / natural killer T (NKT) cells. We found increased expression of T helper (Th)1- over Th2-related cytokines, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-R2/DR5, and several ligands of NK cells in GNMT(-/-) livers. Interestingly, NK cells from GNMT(-/-) mice were spontaneously activated, expressed more TRAIL, and had strong cytotoxic activity, suggesting their contribution to the proinflammatory environment in the liver. Accordingly, NK cells mediated hypersensitivity to concanavalin A (ConA)-mediated hepatitis in GNMT(-/-) mice. Moreover, GNMT(-/-) mice were hypersensitive to endotoxin-mediated liver injury. NK cell depletion and adoptive transfer of TRAIL(-/-) liver-NK cells protected the liver against lipopolysaccharide (LPS) liver damage.
conclusionOur data allow us to conclude that TRAIL-producing NK cells actively contribute to promote a proinflammatory environment at early stages of fatty liver disease, suggesting that this cell compartment may contribute to the progression of NASH.
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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.