Single-cell RNA transcriptomics reveals differences in the immune status of alcoholic and hepatitis B virus-related liver cirrhosis
BackgroundAlcoholic and hepatitis B virus (HBV)-related liver cirrhosis has placed a tremendous burden on the healthcare system with limited treatment options. This study explored the differences in the immune status of alcoholic and HBV-related liver cirrhosis.MethodsA total of 15 human liver sampl...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1132085/full |
| _version_ | 1797935356714156032 |
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| author | Pengpeng Zhang Pengpeng Zhang Hao Li Hao Li Bo Peng Bo Peng Yu Zhang Yu Zhang Kai Liu Kai Liu Ke Cheng Ke Cheng Yingzi Ming Yingzi Ming |
| author_facet | Pengpeng Zhang Pengpeng Zhang Hao Li Hao Li Bo Peng Bo Peng Yu Zhang Yu Zhang Kai Liu Kai Liu Ke Cheng Ke Cheng Yingzi Ming Yingzi Ming |
| author_sort | Pengpeng Zhang |
| collection | DOAJ |
| description | BackgroundAlcoholic and hepatitis B virus (HBV)-related liver cirrhosis has placed a tremendous burden on the healthcare system with limited treatment options. This study explored the differences in the immune status of alcoholic and HBV-related liver cirrhosis.MethodsA total of 15 human liver samples from the Third Xiangya Hospital of Central South University, including five healthy controls (HC group), five alcoholic cirrhosis patients (ALC group), and five HBV-related cirrhosis patients (HBV group) were used. Of these, eight samples, including 3 HC group, 2 ALC group and 3 HBV group, were randomly collected to do single-cell RNA sequencing (scRNA-seq). The degree of steatosis was assessed by H&E staining and the presence of intrahepatic immune cells was evaluated by immunochemistry (IHC).ResultsThe immune status of alcoholic and HBV-related liver cirrhosis differed significantly. ScRNA-seq analysis identified a higher ratio of intrahepatic monocyte/macrophages and an obvious decreased ratio of T cells and B cells in the ALC group than in the HBV group. IHC staining of intrahepatic monocyte/macrophages, T and B cell exhibited similar results with scRNA-seq analysis. CD5L+ Kupffer cells, a cell type involved in lipid metabolism, were the major monocyte/macrophage subset in ALC liver tissue. H&E staining indicated that the level of steatosis was more severe in the ALC than in the HBV group. Ligand/receptor analysis showed that the T cell exhaustion observed in the ALC liver may be related to the expression of Galectin-9 on Kupffer cells. Fewer B cells were also found in the ALC group and most had higher lipid metabolism, reduced ribosomal activity, and a dysregulated mitochondrial oxidative phosphorylation system. Moreover, scRNA-seq showed a significantly lower ratio of plasma B cells, indicating that the humoral immune response in the ALC liver was similarly dysfunctional. Ligand/receptor analysis also discovered that Galectin-9 expressed on Kupffer cells may inhibit humoral immunity.ConclusionPatients with ALC have different immune characteristics than those with HBV-induced cirrhosis, including an increased ratio of intrahepatic monocyte/macrophages and a dysfunctional adaptive immune response in the liver. Galectin-9 could serve as a potential therapeutic target for ALC treatment. |
| first_indexed | 2024-04-10T18:14:15Z |
| format | Article |
| id | doaj.art-f1097828772f43a183936e5492c652ed |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T18:14:15Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-f1097828772f43a183936e5492c652ed2023-02-02T10:09:26ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-02-011410.3389/fendo.2023.11320851132085Single-cell RNA transcriptomics reveals differences in the immune status of alcoholic and hepatitis B virus-related liver cirrhosisPengpeng Zhang0Pengpeng Zhang1Hao Li2Hao Li3Bo Peng4Bo Peng5Yu Zhang6Yu Zhang7Kai Liu8Kai Liu9Ke Cheng10Ke Cheng11Yingzi Ming12Yingzi Ming13The Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaEngineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaEngineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaEngineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaEngineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaEngineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaEngineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaEngineering & Technology Research Center for Transplantation Medicine of National Ministry of Health, Changsha, Hunan, ChinaBackgroundAlcoholic and hepatitis B virus (HBV)-related liver cirrhosis has placed a tremendous burden on the healthcare system with limited treatment options. This study explored the differences in the immune status of alcoholic and HBV-related liver cirrhosis.MethodsA total of 15 human liver samples from the Third Xiangya Hospital of Central South University, including five healthy controls (HC group), five alcoholic cirrhosis patients (ALC group), and five HBV-related cirrhosis patients (HBV group) were used. Of these, eight samples, including 3 HC group, 2 ALC group and 3 HBV group, were randomly collected to do single-cell RNA sequencing (scRNA-seq). The degree of steatosis was assessed by H&E staining and the presence of intrahepatic immune cells was evaluated by immunochemistry (IHC).ResultsThe immune status of alcoholic and HBV-related liver cirrhosis differed significantly. ScRNA-seq analysis identified a higher ratio of intrahepatic monocyte/macrophages and an obvious decreased ratio of T cells and B cells in the ALC group than in the HBV group. IHC staining of intrahepatic monocyte/macrophages, T and B cell exhibited similar results with scRNA-seq analysis. CD5L+ Kupffer cells, a cell type involved in lipid metabolism, were the major monocyte/macrophage subset in ALC liver tissue. H&E staining indicated that the level of steatosis was more severe in the ALC than in the HBV group. Ligand/receptor analysis showed that the T cell exhaustion observed in the ALC liver may be related to the expression of Galectin-9 on Kupffer cells. Fewer B cells were also found in the ALC group and most had higher lipid metabolism, reduced ribosomal activity, and a dysregulated mitochondrial oxidative phosphorylation system. Moreover, scRNA-seq showed a significantly lower ratio of plasma B cells, indicating that the humoral immune response in the ALC liver was similarly dysfunctional. Ligand/receptor analysis also discovered that Galectin-9 expressed on Kupffer cells may inhibit humoral immunity.ConclusionPatients with ALC have different immune characteristics than those with HBV-induced cirrhosis, including an increased ratio of intrahepatic monocyte/macrophages and a dysfunctional adaptive immune response in the liver. Galectin-9 could serve as a potential therapeutic target for ALC treatment.https://www.frontiersin.org/articles/10.3389/fendo.2023.1132085/fullalcoholic liver cirrhosisHBV-related liver cirrhosisscRNA-seqgalectin-9lipid metabolism |
| spellingShingle | Pengpeng Zhang Pengpeng Zhang Hao Li Hao Li Bo Peng Bo Peng Yu Zhang Yu Zhang Kai Liu Kai Liu Ke Cheng Ke Cheng Yingzi Ming Yingzi Ming Single-cell RNA transcriptomics reveals differences in the immune status of alcoholic and hepatitis B virus-related liver cirrhosis Frontiers in Endocrinology alcoholic liver cirrhosis HBV-related liver cirrhosis scRNA-seq galectin-9 lipid metabolism |
| title | Single-cell RNA transcriptomics reveals differences in the immune status of alcoholic and hepatitis B virus-related liver cirrhosis |
| title_full | Single-cell RNA transcriptomics reveals differences in the immune status of alcoholic and hepatitis B virus-related liver cirrhosis |
| title_fullStr | Single-cell RNA transcriptomics reveals differences in the immune status of alcoholic and hepatitis B virus-related liver cirrhosis |
| title_full_unstemmed | Single-cell RNA transcriptomics reveals differences in the immune status of alcoholic and hepatitis B virus-related liver cirrhosis |
| title_short | Single-cell RNA transcriptomics reveals differences in the immune status of alcoholic and hepatitis B virus-related liver cirrhosis |
| title_sort | single cell rna transcriptomics reveals differences in the immune status of alcoholic and hepatitis b virus related liver cirrhosis |
| topic | alcoholic liver cirrhosis HBV-related liver cirrhosis scRNA-seq galectin-9 lipid metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1132085/full |
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