Single-cell RNA sequencing reveals the heterogeneity of liver-resident immune cells in human.
Juanjuan Zhao, Shuye Zhang, Yang Liu, Xiaomeng He, Mengmeng Qu, Gang Xu, Hongbo Wang, Man Huang, Jing Pan, Zhenwen Liu, Zhiwei Li, Lei Liu, Zheng Zhang
Author Information
- Juanjuan Zhao: 1Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112 China.
- Shuye Zhang: 3Shanghai Public Health Clinical Center and Institute of Biomedical Sciences, Fudan University, Shanghai, 201058 China.
- Yang Liu: 1Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112 China.
- Xiaomeng He: 4Research Center for Clinical & Translational Medicine, Fifth Medical Center for General Hospital of PLA, Beijing, 100039 China.
- Mengmeng Qu: 4Research Center for Clinical & Translational Medicine, Fifth Medical Center for General Hospital of PLA, Beijing, 100039 China.
- Gang Xu: 1Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112 China.
- Hongbo Wang: 5Research Center for Liver Transplantation, Fifth Medical Center for General Hospital of PLA, Beijing, 100039 China.
- Man Huang: 1Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112 China.
- Jing Pan: 4Research Center for Clinical & Translational Medicine, Fifth Medical Center for General Hospital of PLA, Beijing, 100039 China.
- Zhenwen Liu: 5Research Center for Liver Transplantation, Fifth Medical Center for General Hospital of PLA, Beijing, 100039 China.
- Zhiwei Li: 6Deparment for Liver Transplantation, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112 China.
- Lei Liu: 1Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112 China.
- Zheng Zhang: 1Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112 China.
The liver plays a critical role in both immune defense and tolerance in the body. The liver-resident immune cells (LrICs) determine the immune properties, but the unique composition and heterogeneity of these cells are incompletely understood. Here, we dissect the diversity of LrICs by a comprehensive transcriptomic profiling using the unbiased single-cell RNA-sequencing (scRNA-seq). A total of 70, 706 of CD45 immune cells from the paired liver perfusion, spleen and peripheral blood as references were profiled. We identified more than 30 discrete cell populations comprising 13 of T and NK cell, 7 of B cell, 4 of plasma cell, and 8 of myeloid cell subsets in human liver and donor-paired spleen and blood, and characterized their tissue distribution, gene expression and functional modules. Especially, four of CXCR6 T and NK cell subsets were found to be present preferentially in the liver, where they manifested heterogeneity, distinct function and prominent homeostatic proliferation. We propose a universal category system of T and NK cells based on distinct chemokine receptors, confirmed subsequently by phenotype, transcriptional factors and functionality. We also identified adaptive changes by the spleen and liver-derived monocyte and macrophage populations. Finally, we give a global glimpse on B cell and plasma cell subsets in human spleen and liver. We, therefore, reveal the heterogeneity and functional diversity of LrICs in human. This study presents comprehensively the landscape of LrICs and will enable further study on their roles in various human diseases.
