IL-25 prevents and cures fulminant hepatitis in mice through a myeloid-derived suppressor cell-dependent mechanism

摘要: Fulminant hepatitis (FH) is a disease characterized by massive destruction of hepatocytes with severe impairment liver function. The pathogenesis FH not fully understood, but hyperactivity T cells and macrophages excessive production cytokines are important hallmarks the condition. In this study, we investigated role interleukin (IL)−25 in FH. IL-25 expression was evaluated patients livers mice induced D-galactosamine (D-Gal) lipopolysaccharide (LPS). Mice were treated before D-Gal/LPS-induced or after concanavalin A (ConA)-induced Mononuclear isolated from without analyzed for GR1+CD11b+ cells. CFSE-labeled cocultured their proliferation flow cytometry. also depleting anti-GR1 antibody D-Gal/LPS administration. constitutively expressed mouse human down-regulated during prevented effect associated increased infiltration coexpressing GR1 CD11b. vitro studies showed that given inhibited T-cell proliferation. Consistently, vivo depletion GR1+ abrogated protective experimental both preventive therapeutic ConA-induced Conclusions: markedly reduced promotes accumulation GR1+CD11b+cells immunoregulatory properties. (Hepatology 2013;58:1436–1450)