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γδ T cells are indispensable for interleukin‐23‐mediated protection against Concanavalin A‐induced hepatitis in hepatitis B virus transgenic mice
Author(s) -
Meng Ziyu,
Wang Jingya,
Yuan Yifang,
Cao Guangchao,
Fan Shuobing,
Gao Chao,
Wang Li,
Li Zheng,
Wu Xiaoli,
Wu Zhenzhou,
Zhao Liqing,
Yin Zhinan
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12712
Subject(s) - concanavalin a , t cell receptor , hepatitis b virus , hbsag , immunology , hepatitis , t cell , biology , microbiology and biotechnology , virus , immune system , biochemistry , in vitro
Summary Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between γδ T cells and liver damage in patients with hepatitis B virus (HBV). However, whether γδ T cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation‐induced hepatitis is unknown. In this study, using HBV transgenic (HBs‐Tg) and HBs‐Tg T‐cell receptor‐ δ ‐deficient (TCR‐ δ −/− ) mice, we found that mice genetically deficient in γδ T cells exhibited more severe liver damage upon Concanavalin A (Con A) treatment, as indicated by substantially higher serum alanine aminotransferase levels, further elevated interferon‐ γ (IFN‐ γ ) levels and more extensive necrosis. γδ T‐cell deficiency resulted in elevated IFN‐ γ in CD4 + T cells but not in natural killer or natural killer T cells. The depletion of CD4 + T cells and neutralization of IFN‐ γ reduced liver damage in HBs‐Tg and HBs‐Tg‐TCR‐ δ −/− mice to a similar extent. Further investigation revealed that HBs‐Tg mice showed an enhanced interleukin‐17 (IL‐17) signature. The administration of exogenous IL‐23 enhanced IL‐17A production from V γ 4 γδ T cells and ameliorated liver damage in HBs‐Tg mice, but not in HBs‐Tg‐TCR‐ δ −/− mice. In summary, our results demonstrated that γδ T cells played a protective role in restraining Con A‐induced hepatitis by inhibiting IFN‐ γ production from CD4 + T cells and are indispensable for IL‐23‐mediated protection against Con A‐induced hepatitis in HBs‐Tg mice. These results provided a potential therapeutic approach for treating the hypersensitivity of HBV carriers to biochemical stimulation‐induced liver damage.