title: Requirement for IRF-1 in the microenvironment supporting development of natural killer cells.
abstract: Natural killer (NK) cells are critical for both innate and adaptive immunity. The development of NK cells requires interactions between their progenitors and the bone-marrow microenvironment; however, little is known about the molecular nature of such interactions. Mice that do not express the transcription factor interferon-regulatory factor-1 (IRF-1; such mice are IRF-1(-/-) mice) have been shown to exhibit a severe NK-cell deficiency. Here we demonstrate that the lack of IRF-1 affects the radiation-resistant cells that constitute the microenvironment required for NK-cell development, but not the NK-cell progenitors themselves. We also show that IRF-1(-/-) bone-marrow cells can generate functional NK cells when cultured with the cytokine interleukin-15 and that the interleukin-15 gene is transcriptionally regulated by IRF-1. These results reveal, for the first time, a molecular mechanism by which the bone-marrow microenvironment supports NK-cell development.
authors.affiliation: Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ogasawara
authors.forename: S
authors.initials: S
authors.lastname: Hida
authors.forename: N
authors.initials: N
authors.lastname: Azimi
authors.forename: Y
authors.initials: Y
authors.lastname: Tagaya
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Yokochi-Fukuda
authors.forename: T A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: S
authors.initials: S
authors.lastname: Taki
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology; D019409:Interleukin-15 / Q000235:genetics / Q000502:physiology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000637:transplantation; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000502:physiology*; D018183:Transplantation Chimera
chemical_list: D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D019409:Interleukin-15; C494258:Irf1 protein, mouse; D008070:Lipopolysaccharides; D010750:Phosphoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; D007371:Interferon-gamma