NKp80 Defines a Critical Step during Human Natural Killer Cell Development

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+ (st...

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Main Authors: 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 III, Michael A. Caligiuri
Format: Article
Language:English
Published: Elsevier 2016-07-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124716307367
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author 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 III
Michael A. Caligiuri
author_facet 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 III
Michael A. Caligiuri
author_sort Aharon G. Freud
collection DOAJ
description 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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spelling doaj.art-61fd41d421fe400498c6b805a85b7b192022-12-22T02:17:19ZengElsevierCell Reports2211-12472016-07-0116237939110.1016/j.celrep.2016.05.095NKp80 Defines a Critical Step during Human Natural Killer Cell DevelopmentAharon G. Freud0Karen A. Keller1Steven D. Scoville2Bethany L. Mundy-Bosse3Stephanie Cheng4Youssef Youssef5Tiffany Hughes6Xiaoli Zhang7Xiaokui Mo8Pierluigi Porcu9Robert A. Baiocchi10Jianhua Yu11William E. Carson III12Michael A. Caligiuri13Department of Pathology, The Ohio State University, Columbus, OH 43210, USADepartment of Pathology, The Ohio State University, Columbus, OH 43210, USAMedical Scientist Training Program, The Ohio State University, Columbus, OH 43210, USADivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USADepartment of Pathology, The Ohio State University, Columbus, OH 43210, USADepartment of Pathology, The Ohio State University, Columbus, OH 43210, USADivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USACenter for Biostatistics, The Ohio State University, Columbus, OH 43210, USACenter for Biostatistics, The Ohio State University, Columbus, OH 43210, USADivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USADivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USADivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USADivision of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, OH 43210, USADivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USAHuman 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.http://www.sciencedirect.com/science/article/pii/S2211124716307367
spellingShingle 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 III
Michael A. Caligiuri
NKp80 Defines a Critical Step during Human Natural Killer Cell Development
Cell Reports
title NKp80 Defines a Critical Step during Human Natural Killer Cell Development
title_full NKp80 Defines a Critical Step during Human Natural Killer Cell Development
title_fullStr NKp80 Defines a Critical Step during Human Natural Killer Cell Development
title_full_unstemmed NKp80 Defines a Critical Step during Human Natural Killer Cell Development
title_short NKp80 Defines a Critical Step during Human Natural Killer Cell Development
title_sort nkp80 defines a critical step during human natural killer cell development
url http://www.sciencedirect.com/science/article/pii/S2211124716307367
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