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

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.

journal_name

J Autoimmun

journal_title

Journal of autoimmunity

authors

Buitrago-Molina LE,Pietrek J,Noyan F,Schlue J,Manns MP,Wedemeyer H,Hardtke-Wolenski M,Jaeckel E

doi

10.1016/j.jaut.2020.102591

subject

Has Abstract

pub_date

2021-02-01 00:00:00

pages

102591

eissn

0896-8411

issn

1095-9157

pii

S0896-8411(20)30226-2

journal_volume

117

pub_type

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