The Detrimental Role of Regulatory T Cells in Nonalcoholic Steatohepatitis.

Autor: Dywicki J; Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany., Buitrago-Molina LE; Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.; Department of Gastroenterology and Hepatology, Essen University Hospital, University Duisburg-Essen, Essen, Germany., Noyan F; Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany., Davalos-Misslitz AC; Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany., Hupa-Breier KL; Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany., Lieber M; Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany., Hapke M; Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany., Schlue J; Institute of Pathology, Hannover Medical School, Hannover, Germany., Falk CS; Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany., Raha S; Institute of Immunology, Hannover Medical School, Hannover, Germany., Prinz I; Institute of Immunology, Hannover Medical School, Hannover, Germany.; Institute of Systems Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Koenecke C; Institute of Immunology, Hannover Medical School, Hannover, Germany.; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany., Manns MP; Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany., Wedemeyer H; Department of Gastroenterology and Hepatology, Essen University Hospital, University Duisburg-Essen, Essen, Germany., Hardtke-Wolenski M; Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.; Department of Gastroenterology and Hepatology, Essen University Hospital, University Duisburg-Essen, Essen, Germany., Jaeckel E; Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
Jazyk: angličtina
Zdroj: Hepatology communications [Hepatol Commun] 2022 Feb; Vol. 6 (2), pp. 320-333. Date of Electronic Publication: 2021 Aug 25.
DOI: 10.1002/hep4.1807
Abstrakt: Nonalcoholic steatohepatitis (NASH) is induced by steatosis and metabolic inflammation. While involvement of the innate immune response has been shown, the role of the adaptive immune response in NASH remains controversial. Likewise, the role of regulatory T cells (Treg) in NASH remains unclear although initial clinical trials aim to target these regulatory responses. High-fat high-carbohydrate (HF-HC) diet feeding of NASH-resistant BALB/c mice as well as the corresponding recombination activating 1 (Rag)-deficient strain was used to induce NASH and to study the role of the adaptive immune response. HF-HC diet feeding induced strong activation of intrahepatic T cells in BALB/c mice, suggesting an antigen-driven effect. In contrast, the effects of the absence of the adaptive immune response was notable. NASH in BALB/c Rag1 -/- mice was substantially worsened and accompanied by a sharp increase of M1-like macrophage numbers. Furthermore, we found an increase in intrahepatic Treg numbers in NASH, but either adoptive Treg transfer or anti-cluster of differentiation (CD)3 therapy unexpectedly increased steatosis and the alanine aminotransferase level without otherwise affecting NASH. Conclusion: Although intrahepatic T cells were activated and marginally clonally expanded in NASH, these effects were counterbalanced by increased Treg numbers. The ablation of adaptive immunity in murine NASH led to marked aggravation of NASH, suggesting that Tregs are not regulators of metabolic inflammation but rather enhance it.
(© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)
Databáze: MEDLINE
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