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
1Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112 China.
2The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518112 China.
Cell Discov. 2020 Apr 28;6:22. doi: 10.1038/s41421-020-0157-z. eCollection 2020.
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.
肝脏在机体的免疫防御和免疫耐受中均发挥着关键作用。肝脏驻留免疫细胞(LrICs)决定了免疫特性,但这些细胞独特的组成和异质性尚未被完全了解。在此,我们通过使用无偏差单细胞RNA测序(scRNA-seq)进行全面的转录组分析,剖析LrICs的多样性。以配对的肝脏灌注、脾脏和外周血中的70,706个CD45免疫细胞作为参考进行分析。我们在人类肝脏以及供体配对的脾脏和血液中鉴定出30多个离散细胞群,包括13个T细胞和自然杀伤(NK)细胞群、7个B细胞群、4个浆细胞群以及8个髓样细胞亚群,并对它们的组织分布、基因表达和功能模块进行了表征。特别地,发现4个CXCR6 T和NK细胞亚群优先存在于肝脏中,它们在肝脏中表现出异质性、独特功能和显著的稳态增殖。我们基于不同的趋化因子受体提出了一个T细胞和NK细胞的通用分类系统,随后通过表型、转录因子和功能得到了证实。我们还鉴定了脾脏和肝脏来源的单核细胞和巨噬细胞群体的适应性变化。最后,我们对人类脾脏和肝脏中的B细胞和浆细胞亚群有了一个全面的了解。因此,我们揭示了人类LrICs的异质性和功能多样性。本研究全面展示了LrICs的全貌,并将有助于进一步研究它们在各种人类疾病中的作用。