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- 2009-10-5
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- 2022-12-28
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PD-L1 Upregulation by IFN-α/γ-mediated Stat1 Suppresses anti-HBV T Cell Response
LanLan Liu 1 2 , Junwei Hou 1 3 , Yuxiu Xu 1 3 , Lijuan Qin 1 3 , Weiwei Liu 1 3 , Han Zhang 1 3 , Yang Li 1 3 , Mi Chen 1 3 , Mengmeng Deng 1 3 , Bao Zhao 1 3 , Jun Hu 1 3 , Huaguo Zheng 1 3 , Changfei Li 1 3 , Songdong Meng 1 3
Affiliations
Affiliations
1
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Center for Biosafety Mega-Science, Chinese Academy of Sciences (CAS), Institute of Microbiology, Beijing, China.
2
Institutes of Physical Science and Information Technology, Anhui University, Hefei, China.
3
University of Chinese Academy of Sciences, Beijing, China.
PMID: 32628668 DOI: 10.1371/journal.pone.0228302
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-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) was then identified as a major transcription factor involved in IFN-α/γ-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-α/γ-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-α and therapeutic vaccines.
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发表于 2020-7-7 12:31