NKp80 Defines a Critical Step during Human Natural Killer Cell Development

Aharon G. Freud; Karen A. Keller; Steven D. Scoville; Bethany L. Mundy-Bosse; Stephanie Cheng; Youssef Youssef; Tiffany Hughes; Xiaoli Zhang; Xiaokui Mo; Pierluigi Porcu; Robert A. Baiocchi; Jianhua Yu; William E. Carson; Michael A. Caligiuri

doi:10.1016/j.celrep.2016.05.095

NKp80 Defines a Critical Step during Human Natural Killer Cell Development

Aharon G. Freud
, Karen A. Keller
, Steven D. Scoville
, Bethany L. Mundy-Bosse
, Stephanie Cheng
, Youssef Youssef
, Tiffany Hughes
, Xiaoli Zhang
, Xiaokui Mo
, Pierluigi Porcu
, Robert A. Baiocchi
, Jianhua Yu
, William E. Carson
, Michael A. Caligiuri

Research output: Contribution to journal › Article › peer-review

104 Scopus citations

Abstract

Human natural killer (NK) cells develop in secondary lymphoid tissues (SLTs) through distinct stages. We identified two SLT lineage (Lin)⁻CD34⁻CD117^+/−CD94⁺CD16⁻ “stage 4” subsets according to expression of the C-type lectin-like surface-activating receptor, NKp80: NKp80⁻ (stage “4a”) and NKp80⁺ (stage “4b”). Whereas stage 4b cells expressed more of the transcription factors T-BET and EOMES, produced interferon-gamma, and were cytotoxic, stage 4a cells expressed more of the transcription factors RORγt and AHR and produced interleukin-22, similar to SLT Lin⁻CD34⁻CD117⁺CD94⁻CD16⁻ “stage 3” cells, whose phenotype overlaps with that of group 3 innate lymphoid cells (ILC3s). Co-culture with dendritic cells or transplantation into immunodeficient mice produced mature NK cells from stage 3 and stage 4a populations. These data identify NKp80 as a marker of NK cell maturity in SLTs and support a model of human NK cell development through a stage 4a intermediate with ILC3-associated features.

Original language	English
Pages (from-to)	379-391
Number of pages	13
Journal	Cell Reports
Volume	16
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2016.05.095
State	Published - Jul 12 2016

Bibliographical note

Publisher Copyright:
© 2016

Funding

This work was supported by NCI grants (MAC) CA095426, CA163205, CA16058, and CA068458 MAC and funds from Pelotonia Fellowship. We thank the Mt. Auburn Ob-Gyn associates and delivery nursing staff at Christ Hospital, the Cell Processing and Manipulation Core in the Translational Cores, and the physicians and nurses at CCHMC for collecting and processing healthy donor UCB and adult BM samples. We also thank the staff at the CHTN from Nationwide Children’s Hospital, Columbus, Ohio as well as at the flow cytometry shared resource from the OSU Comprehensive Cancer Center. We thank Tatiana Oberyszyn for her insightful discussions.

Funders	Funder number
National Childhood Cancer Registry – National Cancer Institute	CA095426, CA163205, CA068458, P30CA016058

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2016.05.095

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title = "NKp80 Defines a Critical Step during Human Natural Killer Cell Development",

abstract = "Human natural killer (NK) cells develop in secondary lymphoid tissues (SLTs) through distinct stages. We identified two SLT lineage (Lin)−CD34−CD117+/−CD94+CD16− {\textquotedblleft}stage 4{\textquotedblright} subsets according to expression of the C-type lectin-like surface-activating receptor, NKp80: NKp80− (stage {\textquotedblleft}4a{\textquotedblright}) and NKp80+ (stage {\textquotedblleft}4b{\textquotedblright}). Whereas stage 4b cells expressed more of the transcription factors T-BET and EOMES, produced interferon-gamma, and were cytotoxic, stage 4a cells expressed more of the transcription factors RORγt and AHR and produced interleukin-22, similar to SLT Lin−CD34−CD117+CD94−CD16− {\textquotedblleft}stage 3{\textquotedblright} cells, whose phenotype overlaps with that of group 3 innate lymphoid cells (ILC3s). Co-culture with dendritic cells or transplantation into immunodeficient mice produced mature NK cells from stage 3 and stage 4a populations. These data identify NKp80 as a marker of NK cell maturity in SLTs and support a model of human NK cell development through a stage 4a intermediate with ILC3-associated features.",

author = "Freud, \{Aharon G.\} and Keller, \{Karen A.\} and Scoville, \{Steven D.\} and Mundy-Bosse, \{Bethany L.\} and Stephanie Cheng and Youssef Youssef and Tiffany Hughes and Xiaoli Zhang and Xiaokui Mo and Pierluigi Porcu and Baiocchi, \{Robert A.\} and Jianhua Yu and Carson, \{William E.\} and Caligiuri, \{Michael A.\}",

note = "Publisher Copyright: {\textcopyright} 2016",

year = "2016",

month = jul,

day = "12",

doi = "10.1016/j.celrep.2016.05.095",

language = "English",

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AU - Cheng, Stephanie

AU - Youssef, Youssef

AU - Hughes, Tiffany

AU - Zhang, Xiaoli

AU - Mo, Xiaokui

AU - Porcu, Pierluigi

AU - Baiocchi, Robert A.

AU - Yu, Jianhua

AU - Carson, William E.

AU - Caligiuri, Michael A.

PY - 2016/7/12

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AB - Human natural killer (NK) cells develop in secondary lymphoid tissues (SLTs) through distinct stages. We identified two SLT lineage (Lin)−CD34−CD117+/−CD94+CD16− “stage 4” subsets according to expression of the C-type lectin-like surface-activating receptor, NKp80: NKp80− (stage “4a”) and NKp80+ (stage “4b”). Whereas stage 4b cells expressed more of the transcription factors T-BET and EOMES, produced interferon-gamma, and were cytotoxic, stage 4a cells expressed more of the transcription factors RORγt and AHR and produced interleukin-22, similar to SLT Lin−CD34−CD117+CD94−CD16− “stage 3” cells, whose phenotype overlaps with that of group 3 innate lymphoid cells (ILC3s). Co-culture with dendritic cells or transplantation into immunodeficient mice produced mature NK cells from stage 3 and stage 4a populations. These data identify NKp80 as a marker of NK cell maturity in SLTs and support a model of human NK cell development through a stage 4a intermediate with ILC3-associated features.

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NKp80 Defines a Critical Step during Human Natural Killer Cell Development

Abstract

Bibliographical note

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ASJC Scopus subject areas

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