1. Immunology and Inflammation
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Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses

  1. Shiho Chiba
  2. Hiroaki Ikushima
  3. Hiroshi Ueki
  4. Hideyuki Yanai
  5. Yoshitaka Kimura
  6. Sho Hangai
  7. Junko Nishio
  8. Hideo Negishi
  9. Tomohiko Tamura
  10. Shinobu Saijo
  11. Yoichiro Iwakura
  12. Tadatsugu Taniguchi  Is a corresponding author
  1. Institute of Industrial Science, The University of Tokyo, Japan
  2. Yokohama City University Graduate School of Medicine, Japan
  3. Medical Mycology Research Center, Chiba University, Japan
  4. Research Institute for Biomedical Sciences, Tokyo University of Science, Japan
Research Article
  • Cited 99
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Cite this article as: eLife 2014;3:e04177 doi: 10.7554/eLife.04177

Abstract

The eradication of tumor cells requires communication to and signaling by cells of the immune system. Natural killer (NK) cells are essential tumor-killing effector cells of the innate immune system; however, little is known about whether or how other immune cells recognize tumor cells to assist NK cells. Here, we show that the innate immune receptor Dectin-1 expressed on dendritic cells and macrophages is critical to NK-mediated killing of tumor cells that express N-glycan structures at high levels. Receptor recognition of these tumor cells causes the activation of the IRF5 transcription factor and downstream gene induction for the full-blown tumoricidal activity of NK cells. Consistent with this, we show exacerbated in vivo tumor growth in mice genetically deficient in either Dectin-1 or IRF5. The critical contribution of Dectin-1 in the recognition of and signaling by tumor cells may offer new insight into the anti-tumor immune system with therapeutic implications.

Article and author information

Author details

  1. Shiho Chiba

    Institute of Industrial Science, The University of Tokyo, Tokyo, Japan
    Competing interests
    No competing interests declared.
  2. Hiroaki Ikushima

    Institute of Industrial Science, The University of Tokyo, Tokyo, Japan
    Competing interests
    No competing interests declared.
  3. Hiroshi Ueki

    Institute of Industrial Science, The University of Tokyo, Tokyo, Japan
    Competing interests
    No competing interests declared.
  4. Hideyuki Yanai

    Institute of Industrial Science, The University of Tokyo, Tokyo, Japan
    Competing interests
    No competing interests declared.
  5. Yoshitaka Kimura

    Institute of Industrial Science, The University of Tokyo, Tokyo, Japan
    Competing interests
    No competing interests declared.
  6. Sho Hangai

    Institute of Industrial Science, The University of Tokyo, Tokyo, Japan
    Competing interests
    No competing interests declared.
  7. Junko Nishio

    Institute of Industrial Science, The University of Tokyo, Tokyo, Japan
    Competing interests
    No competing interests declared.
  8. Hideo Negishi

    Institute of Industrial Science, The University of Tokyo, Tokyo, Japan
    Competing interests
    No competing interests declared.
  9. Tomohiko Tamura

    Yokohama City University Graduate School of Medicine, Yokohama, Japan
    Competing interests
    No competing interests declared.
  10. Shinobu Saijo

    Medical Mycology Research Center, Chiba University, Chiba, Japan
    Competing interests
    No competing interests declared.
  11. Yoichiro Iwakura

    Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan
    Competing interests
    No competing interests declared.
  12. Tadatsugu Taniguchi

    Institute of Industrial Science, The University of Tokyo, Tokyo, Japan
    For correspondence
    tada@m.u-tokyo.ac.jp
    Competing interests
    Tadatsugu Taniguchi, Senior editor, eLife.

Ethics

Animal experimentation: All animal care and experiments conformed to the guidelines for animal experiments of the University of Tokyo, and were approved by the animal research committee of the University of Tokyo (Reference number: P10-122 and P10-123).

Reviewing Editor

  1. Ruslan Medzhitov, Yale University School of Medicine, United States

Publication history

  1. Received: July 28, 2014
  2. Accepted: August 21, 2014
  3. Accepted Manuscript published: August 22, 2014 (version 1)
  4. Version of Record published: September 24, 2014 (version 2)

Copyright

© 2014, Chiba et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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