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Published on: February 18, 2017
Single-cell profiling reveals monocyte heterogeneity and association with liver fibrosis in patients with chronic HBV
Yue Zhuo1,2, Hongzheng Wu3, Wenying Zhao2
1Tianjin Key Laboratory of Pathogenic Microbiology of Infectious Disease, Tianjin Centers for Disease Control and Prevention, Tianjin, China.
Insights
Chronic hepatitis B (CHB) infection drives monocyte expansion and the formation of monocyte-platelet aggregates (MPA). These MPAs contribute to liver inflammation and fibrosis progression in CHB patients.
Area of Science:
- Immunology
- Hepatology
- Molecular Biology
Background:
- Chronic hepatitis B (CHB) causes liver inflammation, fibrosis, and cirrhosis risk.
- Monocyte recruitment to the liver exacerbates fibrosis, but mechanisms are unclear.
Purpose of the Study:
- To investigate the role of circulating monocytes in CHB-associated liver fibrosis.
- To identify molecular mechanisms driving monocyte dysregulation in CHB.
Main Methods:
- Single-cell RNA sequencing of monocytes from CHB patients and healthy controls.
- Validation using conventional techniques.
Main Results:
- Monocytes expanded in CHB patients, with high LIM domain only 2 (LMO2) expression.
- A monocyte subcluster forming monocyte-platelet aggregates (MPA) was increased in CHB.
- MPA frequency correlated with disease markers and showed pro-inflammatory signaling via CCL5.
Conclusions:
- Enhanced LMO2 expression may drive monocyte expansion in CHB.
- Increased MPA subsets contribute to liver fibrosis progression in CHB.
- Findings offer insights into CHB liver fibrosis etiology.
Background:
Chronic hepatitis B (CHB) infection results in persistent liver inflammation, which ultimately leads to liver fibrosis and increases the risk of cirrhosis. Recruitment of circulating monocytes to the liver is an essential aspect that exacerbates liver fibrosis; however, the mechanism underlying their dysregulation, which contributes to this progression, remains unclear.
Methods:
Single-cell RNA sequencing was performed to characterize the landscape of circulating monocytes from patients with CHB and liver fibrosis (CHB group) and healthy controls (HC group). Conventional techniques were performed to validate the findings.
Results:
Monocytes significantly expanded in the CHB group. The proto-oncogene LIM domain only 2 (LMO2) was highly expressed in monocytes from the CHB group, which may be associated with their expansion. In addition, we noticed that a classical monocyte subcluster surged in the CHB group and highly expressed platelet-related genes such as ITGA2B, which was identified as monocyte-platelet aggregates (MPA). The frequency of MPA was significantly higher in the CHB group, positively associated with platelet and white blood cell, and negatively associated with liver fibroscan and age, which indicates that MPA may play an important role in liver inflammation in the early liver fibrosis stage. Moreover, we found that MPA displays the enrichment of chemokine signaling-associated genes, such as C-C chemokine motif ligand 5 (CCL5), and showed an increased adhesion capacity to endothelial cells. After incubation with MPA cell supernatants, pro-inflammatory factors such as IL-8 and IL-1β were upregulated in LX-2 cells, which were reversed by the addition of anti-CCL5 antibodies.
Conclusions:
Our data suggest that enhanced LMO2 expression in circulating monocytes may be associated with their expansion, and an increased MPA subset may participate in liver fibrosis progression. These results provide valuable insights into the etiology of liver fibrosis in patients with CHB.
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