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TICAM-1, an adaptor molecule that participates in Toll-like receptor 3–mediated interferon-β induction

Nature Immunologyvolume 4pages161167 (2003) | Download Citation

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Abstract

Human Toll-like receptor (TLR) 3 recognizes double-stranded (ds) RNA and induces production of interferon (IFN)-β independent of the adaptor molecules MyD88 and TIRAP. Thus, another adaptor must exist that preferentially mediates TLR3-dependent production of IFN-β. We have identified an alternative adaptor, designated Toll-interleukin 1 receptor domain (TIR)-containing adaptor molecule (TICAM)-1, that can physically bind the TIR domain of TLR3 and activate the IFN-β promoter in response to poly(I):poly(C). Thus, dsRNA-TLR3–dependent production of IFN-β is mediated mainly by TICAM-1. This TICAM-1–dependent pathway may have a role in other TLR–IFN-β pathways, which form part of the MyD88-independent cellular immune response.

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Acknowledgements

We thank D.T. Fearon, Y. Murakami and N. Inoue for critical reading of the manuscript; T. Taniguchi and T. Fujita for providing p-125 luc reporter plasmid and anti–IRF-3 Ab, respectively; and S. Akira and K. Miyake for providing MyD88−/− mice and an expression vector for MD-2. This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, and Culture (Scientific Research on Priority Areas), and the Ministry of Health and Welfare, of Japan.

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  1. H.O. and M.M. contributed equally to this work.

Affiliations

  1. Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, Japan

    • Hiroyuki Oshiumi
    • , Misako Matsumoto
    • , Kenji Funami
    • , Takashi Akazawa
    •  & Tsukasa Seya
  2. Department of Molecular Immunology, Nara Institute of Science and Technology, Ikoma, 631-0101, Nara, Japan

    • Kenji Funami
    •  & Tsukasa Seya
  3. CREST, JST (Japan Science and Technology Corporation), Tokyo, 100-0013, Japan

    • Hiroyuki Oshiumi
    • , Misako Matsumoto
    •  & Tsukasa Seya

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The authors declare no competing financial interests.

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Correspondence to Tsukasa Seya.

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https://doi.org/10.1038/ni886

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