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Elevated CD169 expressing monocyte/macrophage promotes systemic inflammation and disease progression in cirrhosis
Lichen Xu1, Chunhong Huang2, Xiaoping Zheng3
1Department of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Insights
CD169-positive monocytes are elevated in cirrhosis, driving inflammation and impacting disease progression. Targeting these cells may offer a new therapeutic strategy for advanced liver disease.
Area of Science:
- Immunology
- Hepatology
- Cell Biology
Background:
- Systemic inflammation is a key factor in advanced cirrhosis progression and prognosis.
- The specific mechanisms initiating inflammation in cirrhosis remain unclear.
- The role of CD169-positive (CD169+) monocytes/macrophages in cirrhotic inflammation is unknown.
Purpose of the Study:
- To investigate the role and function of CD169+ monocytes/macrophages in systemic inflammation associated with advanced cirrhosis.
- To determine if CD169 expression on monocytes correlates with disease severity and inflammatory markers.
- To explore the therapeutic potential of targeting CD169+ monocytes/macrophages in cirrhosis.
Main Methods:
- Flow cytometry was used to analyze CD169+ monocyte percentage, phenotype, and pro-inflammatory function in patient tissues and blood.
- Transcriptome analysis compared CD169+ and CD169- monocytes.
- A mouse model with CD169+ monocyte/macrophage depletion was employed to assess their role in liver injury and fibrosis.
Main Results:
- Cirrhotic patients exhibited increased CD169 expression on monocytes, correlating with inflammatory cytokine levels and disease progression.
- CD169+ monocytes displayed both M1- and M2-like markers, indicating an immune-activated profile.
- CD169+ monocytes were found to inhibit neutrophil apoptosis, and their depletion reduced liver inflammation and necrosis but impaired fibrin resolution.
Conclusions:
- CD169 identifies a subset of monocytes associated with inflammation and disease development in cirrhosis.
- CD169+ monocytes play a significant role in regulating inflammation and tissue repair in liver injury.
- Targeting CD169+ monocytes presents a potential therapeutic avenue for managing inflammation and improving survival in cirrhosis.
Abstract:
Systemic inflammation is related to disease progression and prognosis in patients with advanced cirrhosis. However, the mechanisms underlying the initiation of inflammation are still not fully understood. The role of CD169+ monocyte/macrophage in cirrhotic systemic inflammation was undetected. Flow cytometry analysis was used to detect the percentage and phenotypes of CD169+ monocytes as well as their proinflammatory function in patient-derived cirrhotic tissue and blood. Transcriptome differences between CD169+ and CD169- monocytes were also compared. Additionally, a mouse model with specific depletion of CD169+ monocytes/macrophages was utilized to define their role in liver injury and fibrosis. We observed increased CD169 expression in monocytes from cirrhotic patients, which was correlated with inflammatory cytokine production and disease progression. CD169+ monocytes simultaneously highly expressed M1- and M2-like markers and presented immune-activated profiles. We also proved that CD169+ monocytes robustly prevented neutrophil apoptosis. Depletion of CD169+ monocytes/macrophages significantly inhibited inflammation and liver necrosis in acute liver injury, but the spontaneous fibrin resolution after repeated liver injury was impaired. Our results indicate that CD169 defines a subset of inflammation-associated monocyte that correlates with disease development in patients with cirrhosis. This provides a possible therapeutic target for alleviating inflammation and improving survival in cirrhosis.
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