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

Nature volume 391, pages 700–703 (1998)Cite this article

An Erratum to this article was published on 23 April 1998

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.

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Figure 1: Generation of NK cells from bone-marrow cells upon transfer into irradiated wild-type (WT) mice.
Figure 2: Inability of irradiated IRF-1−/− mice to support NK-cell development from wild-type bone-marrow cells.
Figure 3: In vitro compensation of IRF-1 deficiency by IL-15.
Figure 4: IRF-1 regulates the expression of the IL-15 gene.

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Acknowledgements

We thank N. Tanaka, M. Sato and R. Perlmutter for discussion and M. S. Lamphier for critically reading the manuscript. This work was supported by the Japan Society for the Promotion of Sicnece Research for the Future Program, by a special grant for Advanced Research on Cancer from the Ministry of Education, Science and Culture of Japan, and by the Human Frontier Science Program.

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Authors and Affiliations

  1. Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113, Tokyo, Japan

    Kouetsu Ogasawara, Shigeaki Hida, Takeo Sato, Taeko Yokochi-Fukuda, Tadatsugu Taniguchi & Shinsuke Taki

  2. Metabolism Branch, National Cancer Institute, National Institutes of Health, Building 10, 9000 Rockville Pike, Bethesda, 20892, Maryland, USA

    Nazli Azimi, Yutaka Tagaya & Thomas A. Waldmann

Authors
  1. Kouetsu Ogasawara
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Correspondence to Shinsuke Taki.

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Ogasawara, K., Hida, S., Azimi, N. et al. Requirement for IRF-1 in the microenvironment supporting development of natural killer cells. Nature 391, 700–703 (1998). https://doi.org/10.1038/35636

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