Author:
Dywicki Janine,Buitrago-Molina Laura Elisa,Noyan Fatih,Schlue Jerome,Iordanidis Konstantinos,Manns Michael P.,Wedemeyer Heiner,Jaeckel Elmar,Hardtke-Wolenski Matthias
Abstract
AbstractAutoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease. It is known that AIH originates not from the spleen but from the liver itself. Nonetheless, most details of the etiology and pathophysiology are unknown. We induced experimental murine AIH (emAIH) in NOD/Ltj mice by single administration of a replication-deficient adenovirus and performed splenectomy during late-stage disease. Biochemical disease remission occurred, which was characterized by improvement in transaminase levels. The causes of this remission included a shift in the transcriptomic signature of serum proteins toward regeneration. At the cellular level, there was a marked decrease in activated CD8+T cells and an increase in intrahepatic regulatory T cells (Tregs). Here, intrahepatic Treg numbers correlated with biochemical remission. Notably, an imbalance in the T-cell/B-cell ratio was observed, with a disproportionate increase in total B cells. In summary, intrahepatic increases in Tregs, biochemical remission, and regeneration could be induced by splenectomy in the late stage of emAIH.
Funder
Deutsche Forschungsgemeinschaft
Government of Canada's New Frontiers in Research Fund
European Union’s Horizon 2020 Research and Innovation Program
Medizinische Hochschule Hannover (MHH)
Publisher
Springer Science and Business Media LLC