Single-cell landscape of immune cells during the progression from HBV infection to HBV cirrhosis and HBV-associated hepatocellular carcinoma
IntroductionImmune cells play crucial roles in the development of chronic hepatitis B virus (HBV) infection, leading to cirrhosis and hepatocellular carcinoma (HCC). However, their functions at different disease stages are not fully understood.MethodsIn this study, we used single-cell RNA sequencing...
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| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1320414/full |
| _version_ | 1797403375791243264 |
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| author | Qingquan Bai Qingquan Bai Runyang Li Xiao He Xiaoting Hong Ying Yan Zhengyang Zhao Han Lin Frank Tacke Cornelius Engelmann Cornelius Engelmann Cornelius Engelmann Tianhui Hu Tianhui Hu |
| author_facet | Qingquan Bai Qingquan Bai Runyang Li Xiao He Xiaoting Hong Ying Yan Zhengyang Zhao Han Lin Frank Tacke Cornelius Engelmann Cornelius Engelmann Cornelius Engelmann Tianhui Hu Tianhui Hu |
| author_sort | Qingquan Bai |
| collection | DOAJ |
| description | IntroductionImmune cells play crucial roles in the development of chronic hepatitis B virus (HBV) infection, leading to cirrhosis and hepatocellular carcinoma (HCC). However, their functions at different disease stages are not fully understood.MethodsIn this study, we used single-cell RNA sequencing (scRNA-seq) to characterize the human liver immune microenvironment at different disease stages. We analyzed scRNA-seq data from 118,455 immune cells obtained from livers of six healthy individuals, four patients with HBV infection, five patients with HBV cirrhosis, and three patients with HBV-associated HCC.ResultsOur results showed an accumulation of scar-associated macrophages during disease progression, and we identified two relevant immune subsets, Macrophage-CD9/IL18 and macrophage-CD9/IFI6. Macrophage-CD9/IL18 expanded from HBV infection to cirrhosis, while macrophage-CD9/IFI6 expanded from cirrhosis to HCC. We verified the existence of Macrophage-CD9/IFI6 using multiplex immunofluorescence staining. We also found an increase in cytotoxic NK Cell-GNLY during progression from cirrhosis to HCC. Additionally, the proportion of CD4 T cell-TNFAIP3, CD8 T cell-TNF (effector CD8 T cells), and CD8 T cell-CD53 increased, while the proportion of Treg cells decreased from HBV infection to cirrhosis. The proportion of Treg and CD8 T cell-LAG3 (Exhausted CD8 T cell) enhanced, while the proportion of CD8 T cell-TNF (effector CD8 T cells) decreased from cirrhosis to HCC. Furthermore, GSEA enrichment analyses revealed that MAPK, ERBB, and P53 signaling pathways in myeloid cells were gradually inhibited from HBV infection to cirrhosis and HCC.DiscussionOur study provides important insights into changes in the hepatic immune environment during the progression of HBV-related liver disease, which may help improve the management of HBV-infected liver diseases. |
| first_indexed | 2024-03-09T02:38:12Z |
| format | Article |
| id | doaj.art-29ce181e6f3e40a4ba027be85950592a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-09T02:38:12Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-29ce181e6f3e40a4ba027be85950592a2023-12-06T07:54:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.13204141320414Single-cell landscape of immune cells during the progression from HBV infection to HBV cirrhosis and HBV-associated hepatocellular carcinomaQingquan Bai0Qingquan Bai1Runyang Li2Xiao He3Xiaoting Hong4Ying Yan5Zhengyang Zhao6Han Lin7Frank Tacke8Cornelius Engelmann9Cornelius Engelmann10Cornelius Engelmann11Tianhui Hu12Tianhui Hu13Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, GermanyCancer Research Center, School of Medicine, Xiamen University, Xiamen, ChinaCancer Research Center, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, ChinaCancer Research Center, School of Medicine, Xiamen University, Xiamen, ChinaCancer Research Center, School of Medicine, Xiamen University, Xiamen, ChinaCancer Research Center, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, GermanyDepartment of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, GermanyBerlin Institute of Health - Charité - Universitätsmedizin Berlin, Berlin, GermanyInstitute for Liver and Digestive Health, University College London, London, United KingdomCancer Research Center, School of Medicine, Xiamen University, Xiamen, ChinaShenzhen Research Institute of Xiamen University, Shenzhen, ChinaIntroductionImmune cells play crucial roles in the development of chronic hepatitis B virus (HBV) infection, leading to cirrhosis and hepatocellular carcinoma (HCC). However, their functions at different disease stages are not fully understood.MethodsIn this study, we used single-cell RNA sequencing (scRNA-seq) to characterize the human liver immune microenvironment at different disease stages. We analyzed scRNA-seq data from 118,455 immune cells obtained from livers of six healthy individuals, four patients with HBV infection, five patients with HBV cirrhosis, and three patients with HBV-associated HCC.ResultsOur results showed an accumulation of scar-associated macrophages during disease progression, and we identified two relevant immune subsets, Macrophage-CD9/IL18 and macrophage-CD9/IFI6. Macrophage-CD9/IL18 expanded from HBV infection to cirrhosis, while macrophage-CD9/IFI6 expanded from cirrhosis to HCC. We verified the existence of Macrophage-CD9/IFI6 using multiplex immunofluorescence staining. We also found an increase in cytotoxic NK Cell-GNLY during progression from cirrhosis to HCC. Additionally, the proportion of CD4 T cell-TNFAIP3, CD8 T cell-TNF (effector CD8 T cells), and CD8 T cell-CD53 increased, while the proportion of Treg cells decreased from HBV infection to cirrhosis. The proportion of Treg and CD8 T cell-LAG3 (Exhausted CD8 T cell) enhanced, while the proportion of CD8 T cell-TNF (effector CD8 T cells) decreased from cirrhosis to HCC. Furthermore, GSEA enrichment analyses revealed that MAPK, ERBB, and P53 signaling pathways in myeloid cells were gradually inhibited from HBV infection to cirrhosis and HCC.DiscussionOur study provides important insights into changes in the hepatic immune environment during the progression of HBV-related liver disease, which may help improve the management of HBV-infected liver diseases.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1320414/fullhepatitis BcirrhosisHBV infectionhepatocellular carcinomascRNA-seq |
| spellingShingle | Qingquan Bai Qingquan Bai Runyang Li Xiao He Xiaoting Hong Ying Yan Zhengyang Zhao Han Lin Frank Tacke Cornelius Engelmann Cornelius Engelmann Cornelius Engelmann Tianhui Hu Tianhui Hu Single-cell landscape of immune cells during the progression from HBV infection to HBV cirrhosis and HBV-associated hepatocellular carcinoma Frontiers in Immunology hepatitis B cirrhosis HBV infection hepatocellular carcinoma scRNA-seq |
| title | Single-cell landscape of immune cells during the progression from HBV infection to HBV cirrhosis and HBV-associated hepatocellular carcinoma |
| title_full | Single-cell landscape of immune cells during the progression from HBV infection to HBV cirrhosis and HBV-associated hepatocellular carcinoma |
| title_fullStr | Single-cell landscape of immune cells during the progression from HBV infection to HBV cirrhosis and HBV-associated hepatocellular carcinoma |
| title_full_unstemmed | Single-cell landscape of immune cells during the progression from HBV infection to HBV cirrhosis and HBV-associated hepatocellular carcinoma |
| title_short | Single-cell landscape of immune cells during the progression from HBV infection to HBV cirrhosis and HBV-associated hepatocellular carcinoma |
| title_sort | single cell landscape of immune cells during the progression from hbv infection to hbv cirrhosis and hbv associated hepatocellular carcinoma |
| topic | hepatitis B cirrhosis HBV infection hepatocellular carcinoma scRNA-seq |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1320414/full |
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