Author:
Zhao Juanjuan,Zhang Shuye,Liu Yang,He Xiaomeng,Qu Mengmeng,Xu Gang,Wang Hongbo,Huang Man,Pan Jing,Liu Zhenwen,Li Zhiwei,Liu Lei,Zhang Zheng
Abstract
AbstractThe 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.
Funder
Ministry of Science and Technology of the People's Republic of China
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Genetics,Molecular Biology,Biochemistry
Reference48 articles.
1. Trivedi, P. J. & Adams, D. H. Gut-liver immunity. J. Hepatol. 64, 1187–1189 (2016).
2. Heymann, F. & Tacke, F. Immunology in the liver–from homeostasis to disease. Nat. Rev. Gastroenterol. Hepatol. 13, 88–110 (2016).
3. Gill, U. S., Pallett, L. J., Kennedy, P. T. F. & Maini, M. K. Liver sampling: a vital window into HBV pathogenesis on the path to functional cure. Gut 67, 767–775 (2018).
4. McNamara, H. A. & Cockburn, I. A. The three Rs: recruitment, retention and residence of leukocytes in the liver. Clin. Transl. Immunol. 5, e123 (2016).
5. Gill, U. S. et al. Fine needle aspirates comprehensively sample intrahepatic immunity. Gut 68, 1493–1503 (2019).
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