Single-cell multimodal analysis reveals the dynamic immunopathogenesis of HBV-ACLF progression

Area of Science:

• Immunology
• Hepatology
• Genomics

Background:

• Acute-on-chronic liver failure (ACLF) is a severe condition characterized by immune cell dysfunction.
• Hepatitis B virus (HBV) infection is a common cause of ACLF, leading to significant morbidity and mortality.

Purpose of the Study:

• To comprehensively map the dynamic immune response throughout the disease course of HBV-related ACLF.
• To identify specific immune cell subsets and their roles in disease progression and outcomes.

Main Methods:

• Employed single-cell RNA sequencing and proteomics on peripheral blood mononuclear cells from HBV-ACLF patients and controls.
• Validated findings through in vivo and in vitro functional experiments.

Main Results:

• Identified VCAN+CD14+ monocytes driving early inflammation and CXCR2+ neutrophils and CD163+ monocytes associated with disease deterioration.
• Observed impaired cytotoxic T-cells in progressive ACLF, with CXCR2+ neutrophils inducing T-cell exhaustion.
• Demonstrated therapeutic potential of CXCR2 inhibition in ACLF mouse models.

Conclusions:

• Revealed the dynamic immune evolution in HBV-ACLF through longitudinal multiomics.
• Characterized distinct immune patterns for precise management and therapeutic interventions in HBV-ACLF.