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Buitrago-Molina LE, Pietrek J, Noyan F, et al. Treg-specific IL-2 therapy can reestablish intrahepatic immune regulation in autoimmune hepatitis. J Autoimmun. 2020;117:102591doi: 10.1016/j.jaut.2020.102591.
Buitrago-Molina, L. E., Pietrek, J., Noyan, F., Schlue, J., Manns, M. P., Wedemeyer, H., Hardtke-Wolenski, M., & Jaeckel, E. (2021). Treg-specific IL-2 therapy can reestablish intrahepatic immune regulation in autoimmune hepatitis. Journal of autoimmunity, 117102591. https://doi.org/10.1016/j.jaut.2020.102591
Buitrago-Molina, Laura Elisa, et al. "Treg-specific IL-2 therapy can reestablish intrahepatic immune regulation in autoimmune hepatitis." Journal of autoimmunity vol. 117 (2021): 102591. doi: https://doi.org/10.1016/j.jaut.2020.102591
Buitrago-Molina LE, Pietrek J, Noyan F, Schlue J, Manns MP, Wedemeyer H, Hardtke-Wolenski M, Jaeckel E. Treg-specific IL-2 therapy can reestablish intrahepatic immune regulation in autoimmune hepatitis. J Autoimmun. 2021 Feb;117:102591. doi: 10.1016/j.jaut.2020.102591. Epub 2020 Dec 30. PMID: 33387980.
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J Autoimmun. 2021 Feb;117:102591. doi: 10.1016/j.jaut.2020.102591. Epub 2020 Dec 30.

Treg-specific IL-2 therapy can reestablish intrahepatic immune regulation in autoimmune hepatitis.

Journal of autoimmunity

Laura Elisa Buitrago-Molina, Julia Pietrek, Fatih Noyan, Jerome Schlue, Michael P Manns, Heiner Wedemeyer, Matthias Hardtke-Wolenski, Elmar Jaeckel

Affiliations

  1. Dept. of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, Hannover, Germany; Dept. of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
  2. Dept. of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
  3. Dept. of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, Hannover, Germany.
  4. Inst. of Pathology, Hannover Medical School, Hannover, Germany.
  5. Dept. of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, Hannover, Germany; Dept. of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. Electronic address: [email protected].

PMID: 33387980 DOI: 10.1016/j.jaut.2020.102591

Abstract

Autoimmune hepatitis (AIH) is a chronic autoimmune inflammatory disease that usually requires life-long immunosuppression. Frequent relapses after discontinuation of therapy indicate that intrahepatic immune regulation is not restored by current therapies. As steroid therapy preferentially depletes intrahepatic regulatory T cell (Tregs), immune regulation might be re-established by increasing and functionally strengthening intrahepatic Tregs. In recent clinical trials with low dose IL-2, the Treg compartment was strengthened in autoimmune diseases. Therefore, we tested complexed IL-2/anti-IL-2 to increase the selectivity for Tregs. We used our model of experimental murine AIH (emAIH) and treated the mice with complexed IL-2/anti-Il-2 in the late course of the disease. The mice showed increased intrahepatic and systemic Treg numbers after treatment and a reduction in activated, intrahepatic effector T cells (Teffs). This resulted in a reduction in liver-specific ALT levels and a molecular pattern similar to that of healthy individuals. In conclusion, complexed IL-2/anti-IL-2 restored the balance between Tregs and Teffs within the liver, thereby improving the course of emAIH. Treg-specific IL-2 augmentation offers new hope for reestablishing immune tolerance in patients with AIH.

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Keywords: Autoimmune hepatitis; Low-dose interleukin-2; Regulatory T cells

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