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Requirement for IRF-1 in the microenvironment supporting development of natural killer cells

Author

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  • Kouetsu Ogasawara

    (Graduate School of Medicine and Faculty of Medicine, University of Tokyo)

  • Shigeaki Hida

    (Graduate School of Medicine and Faculty of Medicine, University of Tokyo)

  • Nazli Azimi

    (Metabolism Branch, National Cancer Institute, National Institutes of Health)

  • Yutaka Tagaya

    (Metabolism Branch, National Cancer Institute, National Institutes of Health)

  • Takeo Sato

    (Graduate School of Medicine and Faculty of Medicine, University of Tokyo)

  • Taeko Yokochi-Fukuda

    (Graduate School of Medicine and Faculty of Medicine, University of Tokyo)

  • Thomas A. Waldmann

    (Metabolism Branch, National Cancer Institute, National Institutes of Health)

  • Tadatsugu Taniguchi

    (Graduate School of Medicine and Faculty of Medicine, University of Tokyo)

  • Shinsuke Taki

    (Graduate School of Medicine and Faculty of Medicine, University of Tokyo)

Abstract

Natural killer (NK) cells are critical for both innate and adaptive immunity1,2. The development of NK cells requires interactions between their progenitors and the bone-marrow microenvironment3,4,5,6; 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 deficiency7,8. 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 whencultured with the cytokine interleukin-15 (9-12) 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.

Suggested Citation

  • Kouetsu Ogasawara & Shigeaki Hida & Nazli Azimi & Yutaka Tagaya & Takeo Sato & Taeko Yokochi-Fukuda & Thomas A. Waldmann & Tadatsugu Taniguchi & Shinsuke Taki, 1998. "Requirement for IRF-1 in the microenvironment supporting development of natural killer cells," Nature, Nature, vol. 391(6668), pages 700-703, February.
    • Handle: RePEc:nat:nature:v:391:y:1998:i:6668:d:10.1038_35636
    DOI: 10.1038/35636
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