title: Peripheral natural killer cell maturation depends on the transcription factor Aiolos.
abstract: Natural killer (NK) cells are an innate lymphoid cell lineage characterized by their capacity to provide rapid effector functions, including cytokine production and cytotoxicity. Here, we identify the Ikaros family member, Aiolos, as a regulator of NK-cell maturation. Aiolos expression is initiated at the point of lineage commitment and maintained throughout NK-cell ontogeny. Analysis of cell surface markers representative of distinct stages of peripheral NK-cell maturation revealed that Aiolos was required for the maturation in the spleen of CD11b(high)CD27(-) NK cells. The differentiation block was intrinsic to the NK-cell lineage and resembled that found in mice lacking either T-bet or Blimp1; however, genetic analysis revealed that Aiolos acted independently of all other known regulators of NK-cell differentiation. NK cells lacking Aiolos were strongly hyper-reactive to a variety of NK-cell-mediated tumor models, yet impaired in controlling viral infection, suggesting a regulatory function for CD27(-) NK cells in balancing these two arms of the immune response. These data place Aiolos in the emerging gene regulatory network controlling NK-cell maturation and function.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Holmes
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia Department of Medical Biology, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Huntington
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia.
authors.forename: Rebecca P L
authors.initials: RP
authors.lastname: Thong
authors.affiliation: Cancer Immunology Program, The Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Brady
authors.affiliation: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayakawa
authors.affiliation: Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Nedlands, WA, Australia Centre for Experimental Immunology, Lions Eye Institute, Nedlands, WA, Australia.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Andoniou
authors.affiliation: Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Nedlands, WA, Australia Centre for Experimental Immunology, Lions Eye Institute, Nedlands, WA, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Fleming
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia Department of Computing and Information Systems, University of Melbourne, Parkville, Vic., Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia The Department of Mathematics and Statistics, University of Melbourne, Parkville, Vic., Australia.
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Smyth
authors.affiliation: Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Nedlands, WA, Australia Centre for Experimental Immunology, Lions Eye Institute, Nedlands, WA, Australia.
authors.forename: Mariapia A
authors.initials: MA
authors.lastname: Degli-Esposti
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia Department of Medical Biology, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia Department of Medical Biology, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Axel
authors.initials: A
authors.lastname: Kallies
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia Department of Medical Biology, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Carotta
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, Qld, Australia School of Medicine, University of Queensland, Herston, Qld, Australia.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia Department of Medical Biology, The University of Melbourne, Parkville, Vic., Australia nutt@wehi.edu.au.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D053263:Gene Regulatory Networks / Q000276:immunology; D051740:Ikaros Transcription Factor; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D039481:CD11b Antigen; C491396:Ikzf3 protein, mouse; C513258:Prdm1 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D051740:Ikaros Transcription Factor; D000074462:Positive Regulatory Domain I-Binding Factor 1
keywords: Ikzf3; NK cell; differentiation; transcription