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(-) "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.
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA. Electronic address: aharon.freud@osumc.edu.
authors.forename: Aharon G
authors.initials: AG
authors.lastname: Freud
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Keller
authors.affiliation: Medical Scientist Training Program, The Ohio State University, Columbus, OH 43210, USA; Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Scoville
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Mundy-Bosse
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Youssef
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Hughes
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Mo
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Porcu
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Baiocchi
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology* / Q000637:transplantation; D037181:Lectins, C-Type / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000166:cytology; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D055607:Receptors, Natural Killer Cell / Q000378:metabolism*
chemical_list: C431711:KLRF1 protein, human; D037181:Lectins, C-Type; D055607:Receptors, Natural Killer Cell