title: DNAM-1 expression marks an alternative program of NK cell maturation.
abstract: Natural killer (NK) cells comprise a heterogeneous population of cells important for pathogen defense and cancer surveillance. However, the functional significance of this diversity is not fully understood. Here, we demonstrate through transcriptional profiling and functional studies that the activating receptor DNAM-1 (CD226) identifies two distinct NK cell functional subsets: DNAM-1(+) and DNAM-1(-) NK cells. DNAM-1(+) NK cells produce high levels of inflammatory cytokines, have enhanced interleukin 15 signaling, and proliferate vigorously. By contrast, DNAM-1(-) NK cells that differentiate from DNAM-1(+) NK cells have greater expression of NK-cell-receptor-related genes and are higher producers of MIP1 chemokines. Collectively, our data reveal the existence of a functional program of NK cell maturation marked by DNAM-1 expression.
authors.affiliation: Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia; Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Cancer Research Center of Toulouse (CRCT), Toulouse 31000, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Martinet
authors.affiliation: Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia; Células Inflamatórias e Neoplásicas group, Universidade Federal do Paraná, Curitiba, Paraná 81530-001, Brazil.
authors.forename: Lucas
authors.initials: L
authors.lastname: Ferrari De Andrade
authors.affiliation: Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
authors.forename: Camille
authors.initials: C
authors.lastname: Guillerey
authors.affiliation: Control of Gene Expression Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
authors.forename: Fernando
authors.initials: F
authors.lastname: Souza-Fonseca-Guimaraes
authors.affiliation: Department of Pharmacology, Drug Discovery Biology, Monash Institute of Pharmaceutical, Sciences, Monash University, 399 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Dana S
authors.initials: DS
authors.lastname: Hutchinson
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3050, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Tatiana B
authors.initials: TB
authors.lastname: Kolesnik
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3050, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Nicholson
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3050, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Huntington
authors.affiliation: Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia; School of Medicine, University of Queensland, Herston, QLD 4006, Australia. Electronic address: mark.smyth@qimrberghofer.edu.au.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics* / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D016207:Cytokines; D019409:Interleukin-15; C493277:MAPKAP1 protein, human