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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2020 Feb 16

PMID 32059780

Citations 201

Authors

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

Affiliations

Soon will be listed here.

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.

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References

Sun J, Beilke J, Lanier L . Immune memory redefined: characterizing the longevity of natural killer cells. Immunol Rev. 2010; 236:83-94. PMC: 2907527. DOI: 10.1111/j.1600-065X.2010.00900.x. View

Colonna M, Nakajima H, Navarro F, Lopez-Botet M . A novel family of Ig-like receptors for HLA class I molecules that modulate function of lymphoid and myeloid cells. J Leukoc Biol. 1999; 66(3):375-81. DOI: 10.1002/jlb.66.3.375. View

Scoville S, Freud A, Caligiuri M . Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells. Front Immunol. 2017; 8:360. PMC: 5366880. DOI: 10.3389/fimmu.2017.00360. View

Morvan M, Lanier L . NK cells and cancer: you can teach innate cells new tricks. Nat Rev Cancer. 2015; 16(1):7-19. DOI: 10.1038/nrc.2015.5. View

Kelly J, Darcy P, Markby J, Godfrey D, Takeda K, Yagita H . Induction of tumor-specific T cell memory by NK cell-mediated tumor rejection. Nat Immunol. 2001; 3(1):83-90. DOI: 10.1038/ni746. View

Di Santo J, Vosshenrich C . Bone marrow versus thymic pathways of natural killer cell development. Immunol Rev. 2006; 214:35-46. DOI: 10.1111/j.1600-065X.2006.00461.x. View

Lanier L . Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol. 2008; 9(5):495-502. PMC: 2669298. DOI: 10.1038/ni1581. View

Sun J, Madera S, Bezman N, Beilke J, Kaplan M, Lanier L . Proinflammatory cytokine signaling required for the generation of natural killer cell memory. J Exp Med. 2012; 209(5):947-54. PMC: 3348098. DOI: 10.1084/jem.20111760. View

Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K . Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet. 2000; 356(9244):1795-9. DOI: 10.1016/S0140-6736(00)03231-1. View

10.

Muruganandah V, Sathkumara H, Navarro S, Kupz A . A Systematic Review: The Role of Resident Memory T Cells in Infectious Diseases and Their Relevance for Vaccine Development. Front Immunol. 2018; 9:1574. PMC: 6046459. DOI: 10.3389/fimmu.2018.01574. View

11.

Abel A, Yang C, Thakar M, Malarkannan S . Natural Killer Cells: Development, Maturation, and Clinical Utilization. Front Immunol. 2018; 9:1869. PMC: 6099181. DOI: 10.3389/fimmu.2018.01869. View

12.

Vosshenrich C, Garcia-Ojeda M, Samson-Villeger S, Pasqualetto V, Enault L, Goff O . A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127. Nat Immunol. 2006; 7(11):1217-24. DOI: 10.1038/ni1395. View

13.

Teijaro J, Turner D, Pham Q, Wherry E, Lefrancois L, Farber D . Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J Immunol. 2011; 187(11):5510-4. PMC: 3221837. DOI: 10.4049/jimmunol.1102243. View

14.

Peng H, Tian Z . Diversity of tissue-resident NK cells. Semin Immunol. 2017; 31:3-10. DOI: 10.1016/j.smim.2017.07.006. View

15.

DAndrea A, Kubin M, Trinchieri G . Cooperation of natural killer cell stimulatory factor/interleukin-12 with other stimuli in the induction of cytokines and cytotoxic cell-associated molecules in human T and NK cells. Cell Immunol. 1994; 156(2):480-92. DOI: 10.1006/cimm.1994.1192. View

16.

Kumar B, Ma W, Miron M, Granot T, Guyer R, Carpenter D . Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites. Cell Rep. 2017; 20(12):2921-2934. PMC: 5646692. DOI: 10.1016/j.celrep.2017.08.078. View

17.

Chen E, Tan C, Kou Y, Duan Q, Wang Z, Meirelles G . Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013; 14:128. PMC: 3637064. DOI: 10.1186/1471-2105-14-128. View

18.

OSullivan T, Sun J, Lanier L . Natural Killer Cell Memory. Immunity. 2015; 43(4):634-45. PMC: 4621966. DOI: 10.1016/j.immuni.2015.09.013. View

19.

Vivier E, Artis D, Colonna M, Diefenbach A, Di Santo J, Eberl G . Innate Lymphoid Cells: 10 Years On. Cell. 2018; 174(5):1054-1066. DOI: 10.1016/j.cell.2018.07.017. View

20.

Geissmann F, Cameron T, Sidobre S, Manlongat N, Kronenberg M, Briskin M . Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids. PLoS Biol. 2005; 3(4):e113. PMC: 1073691. DOI: 10.1371/journal.pbio.0030113. View