title: CD24 aggravates acute liver injury in autoimmune hepatitis by promoting IFN-γ production by CD4+T cells.
abstract: The T-cell-mediated immune response is implicated in many clinical hepatic injuries, such as autoimmune hepatitis and acute virus hepatitis. CD24 is widely expressed by different immune cells and plays an important role in the pathogenesis of many autoimmune diseases. However, the role of CD24 in T-cell-mediated liver injury has not been elucidated until now. Here we showed that CD24 deficiency protects mice from concanavalin A (ConA)-induced fulminant liver injury by reducing serum interferon-γ (IFN-γ) levels. CD24 expression by hepatic T cells was markedly increased following ConA challenge. Moreover, decreased IFN-γ production by hepatic CD4+T cells in CD24-deficient mice was detected, which was correlated with downregulated phosphorylation of STAT1 in hepatic tissue. In vitro experiments also supported the conclusion that CD24 deficiency impaired IFN-γ production by CD4+T cells following ConA, CD3/CD28 and phorbol myristate acetate/ionomycin stimulation. Our study suggests that CD24 deficiency confers hepatoprotection by decreasing CD4+T-cell-dependent IFN-γ production in vivo, which suggests that CD24 might be a potential target molecule for reducing clinical hepatitis.
authors.affiliation: Department of Comprehensive Surgery, Clinical Division of South Building, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Chenhong
authors.initials: C
authors.lastname: Zheng
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Shulei
authors.initials: S
authors.lastname: Yin
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Comprehensive Surgery, Clinical Division of South Building, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xie
mesh_terms: D055371:Acute Lung Injury / Q000235:genetics / Q000276:immunology*; D000818:Animals; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003208:Concanavalin A / Q000008:administration & dosage; D004195:Disease Models, Animal; D019693:Hepatitis, Autoimmune / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000276:immunology*; D008213:Lymphocyte Activation; D018345:Mice, Knockout
chemical_list: D051927:CD24 Antigen; D003208:Concanavalin A; D007371:Interferon-gamma