CD300E+ macrophages facilitate liver regeneration after splenectomy in decompensated cirrhotic patients
Abstract Liver cirrhosis is prognostically associated with poor life expectancy owing to subsequent liver failure. Thus, understanding liver regeneration processes during cirrhotic injury is highly important. This study explored the role of macrophage heterogeneity in liver regeneration following sp...
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| Format: | Article |
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Nature Publishing Group
2025-01-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-024-01371-3 |
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| author | Tao Yang Yuan Zhang Chujun Duan Hui Liu Dong Wang Qingshan Liang Xiao Chen Jingchang Ma Kun Cheng Yong Chen Ran Zhuang Jikai Yin |
| author_facet | Tao Yang Yuan Zhang Chujun Duan Hui Liu Dong Wang Qingshan Liang Xiao Chen Jingchang Ma Kun Cheng Yong Chen Ran Zhuang Jikai Yin |
| author_sort | Tao Yang |
| collection | DOAJ |
| description | Abstract Liver cirrhosis is prognostically associated with poor life expectancy owing to subsequent liver failure. Thus, understanding liver regeneration processes during cirrhotic injury is highly important. This study explored the role of macrophage heterogeneity in liver regeneration following splenectomy. We collected detailed clinical information from 54 patients with decompensated cirrhosis before and after splenectomy. Obvious liver regeneration was observed after splenectomy in cirrhotic patients. Single-cell RNA sequencing (scRNA-seq) was performed on three paired liver tissues from patients before and after surgery to explore the immune microenvironment map and the characteristics of liver regeneration-associated macrophages (RAMs). scRNA-seq analysis revealed that the composition of hepatic immune cells changed after splenectomy; among these changes, the proportion of CD300E+ RAMs significantly increased after surgery, and high expression levels of functional genes associated with cell proliferation promoted liver regeneration. Moreover, a mouse model of carbon tetrachloride-induced cirrhosis and a coculture system consisting of primary bone marrow-derived macrophages and hepatocytes were established for validation. We observed a similar phenomenon of liver regeneration in cirrhotic mice and further confirmed that CD300E+ monocyte-derived macrophages facilitated hepatocyte NAD+ synthesis via the secretion of NAMPT, which subsequently promoted hepatocyte proliferation. This study characterized the hepatic immune microenvironment in patients with cirrhosis following splenectomy. Our findings demonstrated that CD300E+ macrophages play a crucial role in remodeling the hepatic immune microenvironment after splenectomy, thereby promoting liver regeneration in patients with decompensated cirrhosis. CD300E+ macrophages are anticipated to emerge as a novel therapeutic strategy for the treatment of liver cirrhosis. |
| format | Article |
| id | doaj-art-10cb4aa95d8a4ca4bf9d1cf087e390ef |
| institution | Kabale University |
| issn | 2092-6413 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-10cb4aa95d8a4ca4bf9d1cf087e390ef2025-02-09T12:14:07ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-01-01571728510.1038/s12276-024-01371-3CD300E+ macrophages facilitate liver regeneration after splenectomy in decompensated cirrhotic patientsTao Yang0Yuan Zhang1Chujun Duan2Hui Liu3Dong Wang4Qingshan Liang5Xiao Chen6Jingchang Ma7Kun Cheng8Yong Chen9Ran Zhuang10Jikai Yin11Department of General Surgery, Tangdu Hospital of the Air Force Medical UniversityDepartment of Immunology, Air Force Medical UniversityDepartment of Immunology, Air Force Medical UniversityDepartment of General Surgery, Tangdu Hospital of the Air Force Medical UniversityDepartment of General Surgery, Tangdu Hospital of the Air Force Medical UniversityDepartment of General Surgery, Tangdu Hospital of the Air Force Medical UniversityDepartment of General Surgery, Tangdu Hospital of the Air Force Medical UniversityDepartment of Immunology, Air Force Medical UniversityDepartment of Immunology, Air Force Medical UniversityDepartment of Hepatobiliary Surgery, Xijing Hospital of the Air Force Medical UniversityDepartment of Immunology, Air Force Medical UniversityDepartment of General Surgery, Tangdu Hospital of the Air Force Medical UniversityAbstract Liver cirrhosis is prognostically associated with poor life expectancy owing to subsequent liver failure. Thus, understanding liver regeneration processes during cirrhotic injury is highly important. This study explored the role of macrophage heterogeneity in liver regeneration following splenectomy. We collected detailed clinical information from 54 patients with decompensated cirrhosis before and after splenectomy. Obvious liver regeneration was observed after splenectomy in cirrhotic patients. Single-cell RNA sequencing (scRNA-seq) was performed on three paired liver tissues from patients before and after surgery to explore the immune microenvironment map and the characteristics of liver regeneration-associated macrophages (RAMs). scRNA-seq analysis revealed that the composition of hepatic immune cells changed after splenectomy; among these changes, the proportion of CD300E+ RAMs significantly increased after surgery, and high expression levels of functional genes associated with cell proliferation promoted liver regeneration. Moreover, a mouse model of carbon tetrachloride-induced cirrhosis and a coculture system consisting of primary bone marrow-derived macrophages and hepatocytes were established for validation. We observed a similar phenomenon of liver regeneration in cirrhotic mice and further confirmed that CD300E+ monocyte-derived macrophages facilitated hepatocyte NAD+ synthesis via the secretion of NAMPT, which subsequently promoted hepatocyte proliferation. This study characterized the hepatic immune microenvironment in patients with cirrhosis following splenectomy. Our findings demonstrated that CD300E+ macrophages play a crucial role in remodeling the hepatic immune microenvironment after splenectomy, thereby promoting liver regeneration in patients with decompensated cirrhosis. CD300E+ macrophages are anticipated to emerge as a novel therapeutic strategy for the treatment of liver cirrhosis.https://doi.org/10.1038/s12276-024-01371-3 |
| spellingShingle | Tao Yang Yuan Zhang Chujun Duan Hui Liu Dong Wang Qingshan Liang Xiao Chen Jingchang Ma Kun Cheng Yong Chen Ran Zhuang Jikai Yin CD300E+ macrophages facilitate liver regeneration after splenectomy in decompensated cirrhotic patients Experimental and Molecular Medicine |
| title | CD300E+ macrophages facilitate liver regeneration after splenectomy in decompensated cirrhotic patients |
| title_full | CD300E+ macrophages facilitate liver regeneration after splenectomy in decompensated cirrhotic patients |
| title_fullStr | CD300E+ macrophages facilitate liver regeneration after splenectomy in decompensated cirrhotic patients |
| title_full_unstemmed | CD300E+ macrophages facilitate liver regeneration after splenectomy in decompensated cirrhotic patients |
| title_short | CD300E+ macrophages facilitate liver regeneration after splenectomy in decompensated cirrhotic patients |
| title_sort | cd300e macrophages facilitate liver regeneration after splenectomy in decompensated cirrhotic patients |
| url | https://doi.org/10.1038/s12276-024-01371-3 |
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