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

Publication date: Available online 13 February 2020Source: CellAuthor(s): 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. FarberSummaryImmune 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 AbstractGrap...

Source: Cell - February 14, 2020 Category: Cytology Source Type: research