Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell. 2020 Feb 20;180(4):749-763.e13. doi: 10.1016/j.cell.2020.01.022. Epub 2020 Feb 13.
Immune responses in diverse tissue sites are critical for protective immunity and homeostasis. Here, we investigate how tissue localization regulates the development and function of human natural killer (NK) cells, innate lymphocytes important for anti-viral and tumor immunity. Integrating high-dimensional analysis of NK cells from blood, lymphoid organs, and mucosal tissue sites from 60 individuals, we identify tissue-specific patterns of NK cell subset distribution, maturation, and function maintained across age and between individuals. Mature and terminally differentiated NK cells with enhanced effector function predominate in blood, bone marrow, spleen, and lungs and exhibit shared transcriptional programs across sites. By contrast, precursor and immature NK cells with reduced effector capacity populate lymph nodes and intestines and exhibit tissue-resident signatures and site-specific adaptations. Together, our results reveal anatomic control of NK cell development and maintenance as tissue-resident populations, whereas mature, terminally differentiated subsets mediate immunosurveillance through diverse peripheral sites. VIDEO ABSTRACT.
不同组织部位的免疫反应对于保护性免疫和体内平衡至关重要。在这里，我们研究了组织定位如何调节人类自然杀伤 (NK) 细胞的发育和功能，NK 细胞是抗病毒和肿瘤免疫的重要先天淋巴细胞。我们整合了来自 60 个人的血液、淋巴器官和黏膜组织部位的 NK 细胞的高维分析，确定了 NK 细胞亚群分布、成熟和功能的组织特异性模式，这些模式在年龄和个体之间得到维持。具有增强效应功能的成熟和终末分化的 NK 细胞在血液、骨髓、脾脏和肺部占优势，并在各部位表现出共享的转录程序。相比之下，具有降低效应能力的前体细胞和不成熟 NK 细胞在淋巴结和肠道中占据优势，并表现出组织驻留特征和特定于部位的适应性。总之，我们的研究结果揭示了 NK 细胞作为组织驻留群体的发育和维持的解剖控制，而成熟、终末分化的亚群通过不同的外周部位介导免疫监视。视频摘要。
