Elevated CD169 expressing monocyte/macrophage promotes systemic inflammation and disease progression 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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
Clinical and experimental medicine - 24(2024), 1 vom: 28. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Lichen [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
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| Anmerkungen: |
© The Author(s) 2024 |
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| doi: |
10.1007/s10238-024-01305-3 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
SPR054926270 |
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| 520 | |a 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. | ||
| 650 | 4 | |a Cirrhosis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Systemic inflammation |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a CD169 |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Huang, Chunhong |4 aut | |
| 700 | 1 | |a Zheng, Xiaoping |4 aut | |
| 700 | 1 | |a Gao, Hainv |4 aut | |
| 700 | 1 | |a Zhang, Sainan |4 aut | |
| 700 | 1 | |a Zhu, Mengfei |4 aut | |
| 700 | 1 | |a Dai, Xiahong |4 aut | |
| 700 | 1 | |a Wang, Gang |4 aut | |
| 700 | 1 | |a Wang, Jie |4 aut | |
| 700 | 1 | |a Chen, Haolu |4 aut | |
| 700 | 1 | |a Zhu, Haihong |4 aut | |
| 700 | 1 | |a Chen, Zhi |4 aut | |
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