Tissue Determinants of Human NK Cell Development, Function, and Residence. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • February 13, 2020

Research

keywords

  • Aging
  • Killer Cells, Natural
  • Lymphopoiesis

Identity

PubMed Central ID

  • PMC7194029

Scopus Document Identifier

  • 85079416349

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2020.01.022

PubMed ID

  • 32059780

Additional Document Info

volume

  • 180

issue

  • 4