近日，美国哥伦比亚大学Donna L. Farber及其小组揭示了人NK细胞发育、功能和驻留的组织决定因素。相关论文2020年2月13日在线发表在《细胞》上。

研究人员探究了组织定位如何调节人类自然杀伤（NK）细胞（这是对抗病毒和肿瘤免疫至关重要的先天淋巴细胞）的发育和功能。整合了来自60名个体的血液、淋巴器官和粘膜组织部位NK细胞的高维分析，研究人员确定了NK细胞亚群的分布、成熟以及不同年龄和个体中功能的组织特异性模式。效应子功能增强的成熟和终末分化NK细胞在血液、骨髓、脾脏和肺中占主导地位，并在各个部位显示出共同的转录程序。相反，效应子能力降低的前体和未成熟NK细胞遍布淋巴结和肠道，并表现出组织驻留特征和部位特异性适应性。总之，这些结果揭示了组织驻留群体中NK的细胞发育和维持，而成熟、终末分化的亚群通过不同的外周位点介导免疫监视。

据介绍，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。

附：英文原文

Title: Tissue Determinants of Human NK Cell Development, Function, and Residence

Author: Pranay Dogra, Chiara Rancan, Wenji Ma, Marta Toth, Takashi Senda, Dustin J. Carpenter, Masaru Kubota, Rei Matsumoto, Puspa Thapa, Peter A. Szabo, Maya Meimei Li Poon, Jacky Li, Janice Arakawa-Hoyt, Yufeng Shen, Lawrence Fong, Lewis L. Lanier, Donna L. Farber

Issue&Volume: February 13, 2020

Abstract: Immune responses in diverse tissue sites are critical for protective immunity andhomeostasis. Here, we investigate how tissue localization regulates the developmentand function of human natural killer (NK) cells, innate lymphocytes important foranti-viral and tumor immunity. Integrating high-dimensional analysis of NK cells fromblood, lymphoid organs, and mucosal tissue sites from 60 individuals, we identifytissue-specific patterns of NK cell subset distribution, maturation, and functionmaintained across age and between individuals. Mature and terminally differentiatedNK cells with enhanced effector function predominate in blood, bone marrow, spleen,and lungs and exhibit shared transcriptional programs across sites. By contrast, precursorand immature NK cells with reduced effector capacity populate lymph nodes and intestinesand exhibit tissue-resident signatures and site-specific adaptations. Together, ourresults reveal anatomic control of NK cell development and maintenance as tissue-residentpopulations, whereas mature, terminally differentiated subsets mediate immunosurveillancethrough diverse peripheral sites.

DOI: 10.1016/j.cell.2020.01.022

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30103-3