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

被引：25

作者：

Liu, LanLan ^{[1
,2
]}

Hou, Junwei ^{[1
,3
]}

Xu, Yuxiu ^{[1
,3
]}

Qin, Lijuan ^{[1
,3
]}

Liu, Weiwei ^{[1
,3
]}

Zhang, Han ^{[1
,3
]}

Li, Yang ^{[1
,3
]}

Chen, Mi ^{[1
,3
]}

Deng, Mengmeng ^{[1
,3
]}

Zhao, Bao ^{[1
,3
]}

Hu, Jun ^{[1
,3
]}

Zheng, Huaguo ^{[1
,3
]}

Li, Changfei ^{[1
,3
]}

Meng, Songdong ^{[1
,3
]}

机构：

[1] Chinese Acad Sci, Inst Microbiol, Ctr Biosafety Megasci, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China

[2] Anhui Univ, Inst Phys Sci & Informat Technol, Hefei, Peoples R China

[3] Univ Chinese Acad Sci, Beijing, Peoples R China

来源：

PLOS ONE | 2020年 / 15卷 / 07期

基金：

中国国家自然科学基金;

关键词：

HEPATITIS-B-VIRUS; INTERFERON-GAMMA; ALPHA; EXPRESSION; INFECTION; PROTEIN; B7-H1; DYSFUNCTION; LYMPHOCYTES; INHIBITION;

D O I：

10.1371/journal.pone.0228302

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-gamma producing T cells in chronic hepatitis B. Currently, IFN-alpha 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-alpha/gamma 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-alpha/gamma-mediated PD-L1 elevation bothin vitroand 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-alpha/gamma-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-alpha and therapeutic vaccines.

引用

页数：17

共 54 条

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