Tissue Determinants of Human NK Cell Development, Function, and Residence
Tissue Determinants of Human NK Cell Development, Function, and Residence
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DOI：
10.1016/j.cell.2020.01.022
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发表时间：
2020-02-20
期刊：
影响因子：
64.5
通讯作者：
Farber, Donna L.
中科院分区：
文献类型：
--
作者：
Dogra, Pranay;Rancan, Chiara;Farber, Donna L.
不同组织部位的免疫应答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，天然淋巴细胞对抗病毒和肿瘤免疫很重要。整合从血液，淋巴器官和粘膜组织部位从60个人的NK细胞的高维分析，我们确定NK细胞亚群的分布，成熟和功能的组织特异性模式保持跨年龄和个体之间。具有增强的效应子功能的成熟和终末分化的NK细胞在血液、骨髓、脾和肺中占主导地位，并且在不同位点之间表现出共享的转录程序。相比之下，具有降低的效应子能力的前体和未成熟NK细胞填充淋巴结和肠，并表现出组织驻留特征和位点特异性适应。总之，我们的研究结果揭示了解剖控制NK细胞的发展和维护组织居民人口，而成熟的，终末分化的子集介导免疫监视通过不同的外周网站。
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.