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

被引：295

作者：

Dogra, Pranay ^{[1
,2
]}

Rancan, Chiara ^{[3
]}

Ma, Wenji ^{[4
]}

Toth, Marta ^{[5
,6
]}

Senda, Takashi ^{[1
,7
]}

Carpenter, Dustin J. ^{[1
,7
]}

Kubota, Masaru ^{[1
,7
]}

Matsumoto, Rei ^{[1
,7
]}

Thapa, Puspa ^{[1
,2
]}

Szabo, Peter A. ^{[1
,2
]}

Poon, Maya Meimei Li ^{[1
]}

Li, Jacky ^{[3
]}

Arakawa-Hoyt, Janice ^{[8
]}

Shen, Yufeng ^{[4
]}

Fong, Lawrence ^{[3
,8
]}

Lanier, Lewis L. ^{[8
,9
]}

Farber, Donna L. ^{[1
,7
,10
]}

机构：

[1] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA

[2] Columbia Univ, Dept Med, Med Ctr, New York, NY 10032 USA

[3] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA 94143 USA

[4] Columbia Univ, Dept Syst Biol, New York, NY 10032 USA

[5] Univ Debrecen, Fac Med, Dept Immunol, Debrecen, Hungary

[6] Univ Debrecen, Doctoral Sch Cell & Immune Biol, Debrecen, Hungary

[7] Columbia Univ, Med Ctr, Dept Surg, New York, NY 10032 USA

[8] Univ Calif San Francisco, Parker Inst Canc Immunotherapy, San Francisco, CA 94143 USA

[9] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA

[10] Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA

来源：

CELL | 2020年 / 180卷 / 04期

基金：

美国国家卫生研究院;

关键词：

NATURAL-KILLER-CELLS; CLASS-I MOLECULES; MEMORY T-CELLS; CYTOMEGALOVIRUS-INFECTION; EXPRESSION; SUBSET; ACTIVATION; CYTOKINE; EXPANSION; RECEPTOR;

D O I：

10.1016/j.cell.2020.01.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：749 / +

页数：28

共 102 条

[1] Natural Killer Cells: Development, Maturation, and Clinical Utilization [J].