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.


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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity / drug effects
  • Biomarkers
  • Computational Biology / methods
  • Disease Management
  • Disease Models, Animal
  • Disease Susceptibility / immunology
  • Gene Expression Profiling
  • Hepatitis, Autoimmune / diagnosis
  • Hepatitis, Autoimmune / etiology*
  • Hepatitis, Autoimmune / metabolism*
  • Hepatitis, Autoimmune / therapy
  • Humans
  • Immunohistochemistry
  • Immunomodulation / drug effects*
  • Immunophenotyping
  • Interleukin-2 / pharmacology*
  • Interleukin-2 / therapeutic use
  • Lymphocyte Count
  • Mice
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*


  • Biomarkers
  • Interleukin-2