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 ro...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.展开更多
基金This work was supported by grants from the Army Technology Research Program of China(BWS12J051)the National Natural Science Foundation of China(31570873)+1 种基金the Shanghai Committee of Science and Technology(2015QA1404700)We thank Professor Guanhong Song and Prof.Xuetao Cao for their critical review of the manuscript.
文摘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.
