RT Journal Article
SR Electronic
T1 Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 153
OP 167
DO 10.1136/gutjnl-2021-325915
VO 72
IS 1
A1 Chao Zhang
A1 Jiesheng Li
A1 Yongqian Cheng
A1 Fanping Meng
A1 Jin-Wen Song
A1 Xing Fan
A1 Hongtao Fan
A1 Jing Li
A1 Yu-Long Fu
A1 Ming-Ju Zhou
A1 Wei Hu
A1 Si-Yu Wang
A1 Yuan-Jie Fu
A1 Ji-Yuan Zhang
A1 Ruo-Nan Xu
A1 Ming Shi
A1 Xueda Hu
A1 Zemin Zhang
A1 Xianwen Ren
A1 Fu-Sheng Wang
YR 2023
UL http://gut.bmj.com/content/72/1/153.abstract
AB Objective A comprehensive immune landscape for HBV infection is pivotal to achieve HBV cure.Design We performed single-cell RNA sequencing of 2 43 000 cells from 46 paired liver and blood samples of 23 individuals, including six immune tolerant, 5 immune active (IA), 3 acute recovery (AR), 3 chronic resolved and 6 HBV-free healthy controls (HCs). Flow cytometry and histological assays were applied in a second HBV cohort for validation.Results Both IA and AR were characterised by high levels of intrahepatic exhausted CD8+ T (Tex) cells. In IA, Tex cells were mainly derived from liver-resident GZMK+ effector memory T cells and self-expansion. By contrast, peripheral CX3CR1+ effector T cells and GZMK+ effector memory T cells were the main source of Tex cells in AR. In IA but not AR, significant cell–cell interactions were observed between Tex cells and regulatory CD4+ T cells, as well as between Tex and FCGR3A+ macrophages. Such interactions were potentially mediated through human leukocyte antigen class I molecules together with their receptors CANX and LILRBs, respectively, contributing to the dysfunction of antiviral immune responses. By contrast, CX3CR1+GNLY+ central memory CD8+ T cells were concurrently expanded in both liver and blood of AR, providing a potential surrogate marker for viral resolution. In clinic, intrahepatic Tex cells were positively correlated with serum alanine aminotransferase levels and histological grading scores.Conclusion Our study dissects the coordinated immune responses for different HBV infection phases and provides a rich resource for fully understanding immunopathogenesis and developing effective therapeutic strategies.Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information, except for the raw data for single-cell RNA sequencing reported in this publication can be accessed under the Gene Expression Omnibus (GSE182159) and the Genome Sequence Archive (https://ngdc.cncb.ac.cn, accession number HRA001730) on request.