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PD-L1 upregulation by IFN-?/?-mediated Stat1 suppresses anti-HBV T cell response.


ABSTRACT: Programmed death ligand 1 (PD-L1) has been recently shown to be a major obstacle to antiviral immunity by binding to its receptor programmed death 1 (PD-1) on specific IFN-? producing T cells in chronic hepatitis B. Currently, IFN-? is widely used to treat hepatitis B virus (HBV) infection, but its antiviral effect vary greatly and the mechanism is not totally clear. We found that IFN-?/? induced a marked increase of PD-L1 expression in hepatocytes. Signal and activators of transcription (Stat1) was then identified as a major transcription factor involved in IFN-?/?-mediated PD-L1 elevation both in vitro and in mice. Blockage of the PD-L1/PD-1 interaction by a specific mAb greatly enhanced HBV-specific T cell activity by the gp96 adjuvanted therapeutic vaccine, and promoted HBV clearance in HBV transgenic mice. Our results demonstrate the IFN-?/?-Stat1-PD-L1 axis plays an important role in mediating T cell hyporesponsiveness and inactivating liver-infiltrating T cells in the hepatic microenvironment. These data raise further potential interest in enhancing the anti-HBV efficacy of IFN-? and therapeutic vaccines.

SUBMITTER: Liu L 

PROVIDER: S-EPMC7337294 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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PD-L1 upregulation by IFN-α/γ-mediated Stat1 suppresses anti-HBV T cell response.

Liu LanLan L   Hou Junwei J   Xu Yuxiu Y   Qin Lijuan L   Liu Weiwei W   Zhang Han H   Li Yang Y   Chen Mi M   Deng Mengmeng M   Zhao Bao B   Hu Jun J   Zheng Huaguo H   Li Changfei C   Meng Songdong S  

PloS one 20200706 7


Programmed death ligand 1 (PD-L1) has been recently shown to be a major obstacle to antiviral immunity by binding to its receptor programmed death 1 (PD-1) on specific IFN-γ producing T cells in chronic hepatitis B. Currently, IFN-α is widely used to treat hepatitis B virus (HBV) infection, but its antiviral effect vary greatly and the mechanism is not totally clear. We found that IFN-α/γ induced a marked increase of PD-L1 expression in hepatocytes. Signal and activators of transcription (Stat1)  ...[more]

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