ArticleCellular and molecular gastroenterology and hepatology2020
Diet Reversal and Immune Modulation Show Key Role for Liver and Adipose Tissue T Cells in Murine Nonalcoholic Steatohepatitis.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 43 citations in OpenAlex.
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- Roles of short-chain fatty acids in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis.World journal of hepatology · 2025Review
- Immunopathogenic mechanisms and immunoregulatory therapies in MASLD.Cellular & molecular immunology · 2025Review
- Dissecting the mechanisms of MASLD fibrosis in the era of single-cell and spatial omics.The Journal of clinical investigation · 2025Review
- Exploring the nonlinear association between cardiometabolic index and hypertension in U.S. Adults: an NHANES-based study.BMC public health · 2025Article
- The microenvironment in the development of MASLD-MASH-HCC and associated therapeutic in MASH-HCC.Frontiers in immunology · 2025Review
- Immunological dynamics in MASH: from landscape analysis to therapeutic intervention.Journal of gastroenterology · 2024Review
- Transcriptomic Landscape Analysis Reveals a Persistent DNA Damage Response in Metabolic Dysfunction-associated Steatohepatitis Post-dietary Intervention.Journal of clinical and translational hepatology · 2024Article
- Ferroptosis is a targetable detrimental factor in metabolic dysfunction-associated steatotic liver disease.Cell death and differentiation · 2024Article
- Spatial genomics: mapping human steatotic liver disease.Nature reviews. Gastroenterology & hepatology · 2024Review
- Unraveling the connection between Hashimoto's Thyroiditis and non-alcoholic fatty liver disease: exploring the role of CD4Endocrine · 2024Article
- Review
- Artificial intelligence-assisted digital pathology for non-alcoholic steatohepatitis: current status and future directions.Journal of hepatology · 2024Review
- Mesenchymal Stem Cell-Derived Exosomes in Various Chronic Liver Diseases: Hype or Hope?Journal of inflammation research · 2024Review
- Shared biomarkers and immune cell infiltration signatures in ulcerative colitis and nonalcoholic steatohepatitis.Scientific reports · 2023Article
- Found in translation-Fibrosis in metabolic dysfunction-associated steatohepatitis (MASH).Science translational medicine · 2023Review
- Review
- Major roles of kupffer cells and macrophages in NAFLD development.Frontiers in endocrinology · 2023Review
- Frontiers and hotspots of adipose tissue and NAFLD: a bibliometric analysis from 2002 to 2022.Frontiers in physiology · 2023Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsNonalcoholic steatohepatitis (NASH) is a multisystem condition, implicating liver and adipose tissue. Although the general involvement of the innate and adaptive immune system has been established, we aimed to define the exact role of the functionally diverse T-cell subsets in NASH pathogenesis through diet reversal and immunologic modulation.
methodsMultiple experimental set-ups were used in 8-week-old C57BL/6J mice, including prolonged high-fat high-fructose diet (HFHFD) feeding, diet reversal from HFHFD to control diet, and administration of anti-CD8a and anti-interleukin 17A antibodies. Plasma alanine aminotransferase, glucose, and lipid levels were determined. Liver and adipose tissue were assessed histologically. Cytotoxic T (Tc), regulatory T, T helper (Th) 1, and Th17 cells were characterized in liver and visceral adipose tissue (VAT) via flow cytometry and RNA analysis.
resultsHFHFD feeding induced the metabolic syndrome and NASH, which coincided with an increase in hepatic Th17, VAT Tc, and VAT Th17 cells, and a decrease in VAT regulatory T cells. Although diet reversal induced a phenotypical metabolic and hepatic normalization, the observed T-cell disruptions persisted. Treatment with anti-CD8a antibodies decreased Tc cell numbers in all investigated tissues and induced a biochemical and histologic attenuation of the HFHFD-induced NASH. Conversely, anti-interleukin 17A antibodies decreased hepatic inflammation without affecting other features of NASH or the metabolic syndrome.
conclusionsHFHFD feeding induces important immune disruptions in multiple hepatic and VAT T-cell subsets, refractory to diet reversal. In particular, VAT Tc cells are critically involved in NASH pathogenesis, linking adipose tissue inflammation to liver disease.
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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.