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Single-cell RNA sequencing reveals intrahepatic immune characteristics related to disease status in HBV-infected patients

ABSTRACT: Objective: A comprehensive view of the intrahepatic immune responses to HBV infection at the single-cell resolution is pivotal to HBV cure. Design We performed single-cell RNA sequencing (scRNA-seq) of 243,000 cells from 46 paired liver and blood samples of 23 individuals, including 6 immune tolerant (IT), 5 immune active (IA), 3 acute resolved (AR), 3 chronic resolved (CR), and 6 HBV-free healthy controls (HC). Results Both IA and AR were characterized by high levels of intrahepatic exhausted CD8+ T (Tex) cells, which were absent or rarely found in HC, CR, and IT. 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 interactions were observed between Tex cells and regulatory CD4+ T cells together with FCGR3A+ macrophages, of which HLA-B and HLA-I together with their receptors CANX and LILR, respectively, may constitute the main axes mediating such cellular interactions. Clinically, intrahepatic Tex cells were positively correlated with serum ALT levels and histological grading scores. By contrast, CX3CR1+ CD8+ T cells were clonally expanded in both liver and blood of AR and showed high consistency, providing a valid surrogate marker candidate for predicting HBV clearance. Conclusion: Our study dissects the coordinated immune response in relation to disease status and provides a rich resource for understanding immunopathogenesis and developing effective therapeutic strategies for chronic hepatitis B.

ORGANISM(S): Homo sapiens

PROVIDER: GSE182159 | GEO | 2022/04/05

REPOSITORIES: GEO

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