title: Interferon-gamma negatively regulates Th17-mediated immunopathology during mouse hepatitis virus infection.
abstract: Fulminant hepatitis can cause acute liver failure and death in both humans and mice. However, the cellular and molecular mechanisms underlying the acute disease are still not well understood. Here, we examine the role of Th17 response in the development of the acute hepatitis following infection with mouse hepatitis virus (MHV). We show that IL-17 levels in serum are rapidly elevated and positively correlated to liver damage and death of the mice. In IFN-γR(-/-) mice, Th17 response is enhanced and the elevated IL-17 production contributes to severe liver damage as well as detrimental inflammation because neutralization of IL-17 effectively suppresses inflammation and protects mice from liver injury. We further show that IFN-γ facilitates antigen-induced apoptosis of Th17 cells and adoptive transferred IFN-γR(-/-), but not IFN-γR(+/+); CD4(+) T cells promotes an enhanced liver damage in wild-type mice. The results demonstrate an essential role of Th17 cells in MHV-induced immunopathology and the importance of IFN-γ in maintaining immune balance between Th1 and Th17 responses during acute viral infection.
authors.affiliation: National Laboratory of Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Xilai
authors.initials: X
authors.lastname: Ding
authors.forename: Jingjing
authors.initials: J
authors.lastname: Deng
authors.forename: Yu
authors.initials: Y
authors.lastname: Lu
authors.forename: Zene
authors.initials: Z
authors.lastname: Matsuda
authors.forename: Andreas
authors.initials: A
authors.lastname: Thiel
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
authors.forename: Hongyu
authors.initials: H
authors.lastname: Deng
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Qin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006524:Hepatitis, Viral, Animal / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D020381:Interleukin-17 / Q000097:blood / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000276:immunology*; D016019:Survival Analysis; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D007371:Interferon-gamma