Diet Reversal and Immune Modulation Show Key Role for Liver and Adipose Tissue T Cells in Murine Nonalcoholic SteatohepatitisSummary
| Autor: | Wilhelmus J. Kwanten, Thomas Vanwolleghem, Sven Francque, Joris G. De Man, Didier G. Ebo, Mikhaïl A. Van Herck, Lucio Gama, Luisa Vonghia, Yvon Julé, Benedicte Y. De Winter, Peter Michielsen |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
T-Lymphocytes Adipose tissue PPAR peroxisome proliferator-activated receptor Regulatory T Cells Pathogenesis Liver disease Mice 0302 clinical medicine Non-alcoholic Fatty Liver Disease Cytotoxic T cell Adipose Tissue Inflammation Original Research Gastroenterology HFHFD high-fat high-fructose diet VAT visceral adipose tissue Cytotoxic T Cells Acquired immune system Adipose Tissue 030211 gastroenterology & hepatology CD control diet medicine.symptom NASH nonalcoholic steatohepatitis medicine.medical_specialty DR diet reversal ITT insulin tolerance testing Inflammation Tc cytotoxic T 03 medical and health sciences Immune system T Helper 1 Cells Internal medicine ALT alanine aminotransferase medicine Animals lcsh:RC799-869 Th T helper Hepatology GTT glucose tolerance testing business.industry SAT subcutaneous adipose tissue nutritional and metabolic diseases medicine.disease IL interleukin Diet T Helper 17 Cells 030104 developmental biology Endocrinology Treg regulatory T MT Masson’s trichrome lcsh:Diseases of the digestive system. Gastroenterology Human medicine NAFLD nonalcoholic fatty liver disease Metabolic syndrome business NAS nonalcoholic fatty liver disease activity score |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology, Vol 10, Iss 3, Pp 467-490 (2020) Cellular and Molecular Gastroenterology and Hepatology CMGH Cellular and Molecular Gastroenterology and Hepatology |
| ISSN: | 2352-345X |
| Popis: | Background & Aims Nonalcoholic 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. Methods Multiple 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. Results HFHFD 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. Conclusions HFHFD 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. Graphical abstract |
| Databáze: | OpenAIRE |
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