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Buitrago-Molina, Laura Elisa; Pietrek, Julia; Noyan, Fatih; Schlue, Jerome; Manns, Michael P.; Wedemeyer, Heiner; Hardtke-Wolenski, Matthias; Jaeckel, Elmar
Journal of autoimmunity, February 2021, 2021-02-00, 20210201, Volume: 117Journal Article
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. •Treg numbers are massively increased after ldIL-2 treatment.•LdIL-2 treatment induces long lasting increase of Tregs.•Complexed IL-2 restores the balance between Tregs and Teffs within the liver.•LdIL-2 treatment ameliorates emAIH.
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