ArticleHepatology (Baltimore, Md.)2014
Activation of invariant natural killer T cells impedes liver regeneration by way of both IFN-γ- and IL-4-dependent mechanisms.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 42 citations in OpenAlex.
- Immunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease.Cellular & molecular immunology · 2025Review
- [Research progress on the role of invariant natural killer T cells in immune-mediated liver injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Innate immune regulation in inflammation resolution and liver regeneration in drug-induced liver injury.Archives of toxicology · 2025Review
- Article
- Soluble CD46 as a diagnostic marker of hepatic steatosis.EBioMedicine · 2024Article
- Immunity from NK Cell Subsets Is Important for Vaccine-Mediated Protection in HPV+ Cancers.Vaccines · 2024Article
- Ten-eleven translocation-2-mediated macrophage activation promotes liver regeneration.Cell communication and signaling : CCS · 2024Article
- Responses of hepatic sinusoidal cells to liver ischemia-reperfusion injury.Frontiers in cell and developmental biology · 2023Review
- Myeloid peroxisome proliferator-activated receptor α deficiency accelerates liver regeneration via IL-6/STAT3 pathway after 2/3 partial hepatectomy in mice.Hepatobiliary surgery and nutrition · 2022Article
- Familial hemophagocytic lymphohistiocytosis hepatitis is mediated by IFN-γ in a predominantly hepatic-intrinsic manner.PloS one · 2022Article
- Activation of iNKT Cells Facilitates Liver Repair After Hepatic Ischemia Reperfusion Injury Through Acceleration of Macrophage Polarization.Frontiers in immunology · 2021Article
- Review
- IL-23 mediates murine liver transplantation ischemia-reperfusion injury via IFN-γ/IRF-1 pathway.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Tissue-specific functions of invariant natural killer T cells.Nature reviews. Immunology · 2018Review
- Targeting inflammation for the treatment of alcoholic liver disease.Pharmacology & therapeutics · 2017Review
- Modulation of liver regeneration via myeloid PTEN deficiency.Cell death & disease · 2017Article
- Update on the Mechanisms of Liver Regeneration.Seminars in liver disease · 2017Review
- Liver regeneration microenvironment of hepatocellular carcinoma for prevention and therapy.Oncotarget · 2017Review
- The dynamic changes of circulating invariant natural killer T cells during chronic hepatitis B virus infection.Hepatology international · 2016Article
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7 authors at 3 institutions in 2 countries.
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Abstract
unlabelledInvariant natural killer T (iNKT) cells are a major subset of lymphocytes found in the liver. These cells mediate various functions, including hepatic injury, fibrogenesis, and carcinogenesis. However, the function of iNKT cells in liver regeneration remains unclear. In the present study, partial hepatectomy (PHx) was used to study liver regeneration. α-Galactosylceramide (α-GalCer), a specific ligand for iNKT cells, was used to induce iNKT cell activation. After PHx, two strains of iNKT cell-deficient mice, CD1d(-/-) and Jα281(-/-) mice, showed normal liver regeneration. Injection of α-GalCer before or after PHx, which rapidly stimulated interferon-gamma (IFN-γ) and interleukin (IL)-4 production by iNKT cells, markedly inhibited liver regeneration. In vitro treatment with IFN-γ inhibited hepatocyte proliferation. In agreement with this in vitro finding, genetic disruption of IFN-γ or its downstream signaling molecule signal transducer and activator of transcription (STAT)1 significantly abolished the α-GalCer-mediated inhibition of liver regeneration. In vitro exposure to IL-4 did not affect hepatocyte proliferation, but surprisingly, genetic ablation of IL-4 or its downstream signaling molecule STAT6 partially eliminated the inhibitory effect of α-GalCer on liver regeneration. Further studies revealed that IL-4 contributed to α-GalCer-induced iNKT cell expansion and IFN-γ production, thereby inhibiting liver regeneration.
conclusioniNKT cells play a minor role in controlling liver regeneration after PHx under healthy conditions. Activation of iNKT cells by α-GalCer induces the production of IFN-γ, which directly inhibits liver regeneration, and IL-4, which indirectly attenuates liver regeneration by stimulating iNKT cell expansion and IFN-γ production.
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