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2013 Fiscal Year Final Research Report

Spatiotemporal regulation of nucleic acid uptake and signaling

Research Project

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Project/Area Number 23590558
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Immunology
Research InstitutionHokkaido University

Principal Investigator

MATSUMOTO Misako  北海道大学, 医学(系)研究科(研究院), 特任准教授 (30332456)

Co-Investigator(Renkei-kenkyūsha) SEYA Tsukasa  北海道大学, 大学院医学研究科, 教授 (10301805)
Project Period (FY) 2011 – 2013
Keywords自然免疫 / Toll-like receptor / エンドソーム / 樹状細胞 / RNA認識 / ウイルス感染 / 炎症応答 / マクロファージ
Research Abstract

Endosomal Toll-like receptor (TLR) 3 serves as a sensor of viral infection and sterile tissue necrosis and activates innate and adaptive immunity. Although TLR3 recognizes double-stranded (ds) RNA, little is known about structural features of virus- or host-derived RNAs that activate TLR3 in infection/inflammatory states. In this study, we demonstrate that single-stranded RNAs harboring stable incomplete stem structures are potent TLR3 agonists. Like poly(I:C), a synthetic dsRNA, these structured RNAs were internalized into cells via raftlin-mediated endocytosis and activated TLR3. Based on the ligand recognition mode of TLR3 and uptake mechanism of extracellular nucleic acids, we have generated novel TLR3 ligand that activates endosomal TLR3 but not cytoplasmic RNA sensors.

  • Research Products

    (56 results)

All 2014 2013 2012 2011

All Journal Article (40 results) Presentation (14 results) Book (2 results)

  • [Journal Article] IPS-1 is essential for type III interferon production by hepatocytes and dendritic cells in response to hepatitis C virus infection2014

    • Author(s)
      Okamoto, M., H. Oshiumi, M. Azuma, M. Matsumoto, and T. Seya.
    • Journal Title

      J . Immunol

      Volume: 192(6) Pages: 2770-2777

  • [Journal Article] Myeloid-derived suppressor cells confer tumor-suppressive functions on natural killer cells via polyinosinic : polycytidylic acid treatment in mouse tumor model2014

    • Author(s)
      Shime, H., A. Kojima, A. Maruyama, Y. Saito, H. Oshiumi, M. Matsumoto, and T. Seya.
    • Journal Title

      J . Innate. Immun

      Volume: 6 Pages: 293-305

  • [Journal Article] The N-terminal domain of TIR domain-containing adaptor molecule-1, TICAM-12014

    • Author(s)
      Kumeta, H., H. Sakakibara, Y. Enokizono, K. Ogura, M. Horiuchi, M. Matsumoto, T. Seya, and F. Inagaki.
    • Journal Title

      J. Biomolec. NMR

      Volume: 58(3) Pages: 227-230

  • [Journal Article] Beyond double-stranded RNA : TLR3 signaling in RNA-induced immune responses2014

    • Author(s)
      Tatematsu M, T. Seya, and M. Matsumoto.
    • Journal Title

      Biochem. J .

      Volume: 458 (2) Pages: 195-201

  • [Journal Article] Cell type-specific subcellular localization of phospho-TBK1 in response to cytoplasmic viral DNA2013

    • Author(s)
      Suzuki, T., H. Oshiumi, M. Miyashita, H. H. Aly, M. Matsumoto, and T. Seya.
    • Journal Title

      PLos ONE

      Volume: 8(12) Pages: e83639

  • [Journal Article] Structures and interface mapping of the TIR-domain-containing adaptor molecules involved in interferon signaling2013

    • Author(s)
      Enokizono, Y., H. Kumeta, K. Funami, M. Horiuchi, J. Sarmiento, K. Yamashita, D. Standley, M. Matsumoto, T. Seya, and F. Inagaki.
    • Journal Title

      Proc. Natl. Acad. Sci. U. S. A.

      Volume: 110(49) Pages: 19908-19913

  • [Journal Article] The MyD88 pathway in plasmacytoid and CD4^+ dendritic cells primarily triggers type I interferon production against measles virus in a mouse infection model2013

    • Author(s)
      Takaki, H., M. Takeda, M. Tahara, M. Shingai, Oshiumi, M. Matsumoto, and T. Seya.
    • Journal Title

      J . Immunol

      Volume: 191(9) Pages: 4740-4747

  • [Journal Article] MAVS-dependent IRF3/7 bypass of interferon b-induction restricts the response to measles infection in CD150Tg mouse bone marrow-derived dendritic cells2013

    • Author(s)
      Takaki, H., K. Honada, K. Atarashi, F. Kobayashi, T. Ebihara, H. Oshiumi, M. Matsumoto, M. Shingai, and T. Seya.
    • Journal Title

      Mol Immunol

      Volume: 57(2) Pages: 100-110

  • [Journal Article] A Distinct role of Riplet-mediated K63-linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses2013

    • Author(s)
      Oshiumi, H., M. Miyashita, M. Matsumoto, and T. Seya.
    • Journal Title

      PLoS Pathog

      Volume: 9(8) Pages: e1003533

  • [Journal Article] Toll-like receptor 3 recognizes incomplete stem structures in single-stranded viral RNA2013

    • Author(s)
      Tatematsu, M., F. Nishikawa, T. Seya, and M. Matsumoto.
    • Journal Title

      Nat. Commun

      Volume: 4 Pages: 1833

  • [Journal Article] Cleaved/associated TLR3 represents the primary form of the signaling receptor2013

    • Author(s)
      Toscano F., Y. Estornes, F. Virard, A. Garcia-Cattaneo, A. Pierrot, B. Vanbervliet, M. Bonnin, M. J. Ciancanelli, S-Y. Zhang, K. Funami, T. Seya, M. Matsumoto, J-J. Pin, J-L. Casanova, T. Renno, and S. Lebecque.
    • Journal Title

      J Immunol

      Volume: 190(2) Pages: 764-773

  • [Journal Article] Targeting TLR3 with no RIG-I/MDA5 activation is effective in immunotherapy for cancer2013

    • Author(s)
      Seya T., M. Azuma, and M. Matsumoto.
    • Journal Title

      Expert Opin. Ther. Targets

      Volume: 17(5) Pages: 533-544

  • [Journal Article] Multi-step regulation of interferon induction by hepatitis C virus2013

    • Author(s)
      Oshiumi H., K. Funami, H. H. Aly, M. Matsumoto, and T. Seya.
    • Journal Title

      Arch Immunol Ther Exp (Warsz)

      Volume: 61(2) Pages: 127-138

  • [Journal Article] 抗がん免疫アジュバント:歴史から現状まで2013

    • Author(s)
      瀬谷司、松本美佐子
    • Journal Title

      実験医学

      Volume: 31(12) Pages: 107-113

  • [Journal Article] TLR3免疫アジュバントの開発2013

    • Author(s)
      松本美佐子、瀬谷司
    • Journal Title

      医学のあゆみ

      Volume: 244(9) Pages: 794-799

  • [Journal Article] Cross-priming for anti-tumor CTL induced by soluble Ag + polyI : C depends on the TICAM-1 pathway in mouse CD11c+/CD8a+ dendritic cells2012

    • Author(s)
      Azuma, M., T. Ebihara, H. Oshiumi, M. Matsumoto, and T. Seya.
    • Journal Title

      Oncoimmunology

      Volume: 1(5) Pages: 581-592

  • [Journal Article] Dendritic cells from oral cavity induce Foxp3^+ regulatory T cells upon antigen stimulation2012

    • Author(s)
      Yamazaki S., A, Maruyama, K. Okada, M. Matsumoto, A. Morita, and T. Seya.
    • Journal Title

      PLoS ONE

      Volume: 7(12) Pages: e51665

  • [Journal Article] Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors2012

    • Author(s)
      Shime, H., M. Matsumoto, H. Oshiumi, S. Tanaka, A. Nakane, Y. Iwakura, H. Tahara, N. Inoue, T. Seya.
    • Journal Title

      Proc. Natl. Acad. Sci. U. S. A.

      Volume: 109(6) Pages: 2066-2071

  • [Journal Article] Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes2012

    • Author(s)
      Naito, A. T., T. Sumida, S. Nomura, M-L Liu, T. Higo, K. A. Nakagawa, Okada, T. Sakai, A. A. Hashimoto, Y. Hara, I. Shimizu, W. Zhu, H. Toko, A. Katada, H. Akazawa, T. Oka, J-K. Lee, T. Minamino, T. Nagai, K. Walsh, A. Kikuchi, M. Matsumoto, M. Botto, I. Shiojima, and I. Komuro.
    • Journal Title

      Cell

      Volume: 149(6) Pages: 1298-1313

  • [Journal Article] The Toll-like receptor 3-mediayed antiviral response is important for protection against poliovirus infection in poliovirus receptor transgenic mice2012

    • Author(s)
      Abe, Y., K. Fujii, N. Nagata, O. Takeuchi, S. Akira, H. Oshiumi, M. Matsumoto, T. Seya, and S. Koike.
    • Journal Title

      J . Virol

      Volume: 86(1) Pages: 185-194

  • [Journal Article] TLR3/TICAM-1 signaling in tumor cell RIP3-dependent necroptosis2012

    • Author(s)
      Seya, T., H. Shime, H. Takaki, M. Azuma, H. Oshiumi, and M. Matsumoto.
    • Journal Title

      Oncoimmunology

      Volume: 1(6) Pages: 917-923

  • [Journal Article] 自然免疫と癌治療2012

    • Author(s)
      瀬谷司、松本美佐子
    • Journal Title

      医学のあゆみ

      Volume: 243 (1) Pages: 115-121

  • [Journal Article] ネクローシス細胞による炎症惹起の機序2012

    • Author(s)
      瀬谷司、志馬寛明、松本美佐子
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 57(6) Pages: 674-680

  • [Journal Article] ウイルス感染による自然免疫活性化機構2012

    • Author(s)
      松本美佐子、押海裕之、瀬谷司
    • Journal Title

      炎症と免疫先端医学社

      Volume: 20(1) Pages: 3-8

  • [Journal Article] UNC93B1 physically associates with human TLR8 and regulates TLR8-mediated signaling2011

    • Author(s)
      Itoh, H., M. Tatematsu, A. Watanabe, K. Iwano. K. Funami, T. Seya and M. Matsumoto.
    • Journal Title

      PLoS ONE

      Volume: 6(12) Pages: e28500

  • [Journal Article] Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency2011

    • Author(s)
      Sancho-Shimizu V, Pérez de Diego R, Lorenzo L, Seya T, Matsumoto M, et al.
    • Journal Title

      J . Clin. Invest

      Volume: 121(12) Pages: 4889-4902

  • [Journal Article] The TLR3-TICAM-1 pathway is mandatory for innate immune responses to poliovirus infection2011

    • Author(s)
      Oshiumi, H., M. Okamoto, K. Fujii, T. Kawanishi, M. Matsumoto, S. Koike, and T. Seya.
    • Journal Title

      J . Immunol

      Volume: 15; 187 Pages: 5320-5327

  • [Journal Article] Phosphoinositide 3-kinaseg controls the intracellular localization of CpG to limit DNA-PKcs-dependent IL-10 production in macrophages2011

    • Author(s)
      Hazeki, K., Y. Kametani, H. Murakami, M. Uehara, Y. Ishikawa, K. Nigorokawa, S. Takasuga, T. Sasaki, T. Seya, M. Matsumoto, and O. Hazeki.
    • Journal Title

      PLoS ONE

      Volume: 6 (10) Pages: e26836

    • DOI

      10.1371/journal.pone.0026836

  • [Journal Article] DDX60, a DHXD/H box helicase, is a novel antiviral factor promoting RIG-I-like receptor-mediated signaling2011

    • Author(s)
      Miyashita, M., H. Oshiumi, M. Matsumoto, and T. Seya.
    • Journal Title

      Mol. Cell Biol

      Volume: 31(18) Pages: 3802-3819

  • [Journal Article] Development of mouse hepatocyte lines permissive for hepatitis C virus (HCV)2011

    • Author(s)
      Aly, H. H., H. Oshiumi, H. Shime, M. Matsumoto, T. Wakita, K. Shimotohno, and T. Seya.
    • Journal Title

      Plos ONE

      Volume: 6 (6) Pages: e21284

  • [Journal Article] Development of monoclonal antibodies that specifically interact with necrotic lymphoma cells2011

    • Author(s)
      Wakasa K., H. Shime, M. Kurita-Taniguchi, M. Matsumoto, M. Imamura, and T. Seya.
    • Journal Title

      Microbiol. Immunol

      Volume: 55(5) Pages: 373-377

  • [Journal Article] TLR2-dependent induction of IL-10 and Foxp3^+CD25^+CD4^+ regulatory T cells prevents effective anti-tumor immunity induced by Pam2 lipopeptides in vivo2011

    • Author(s)
      Yamazaki S., K. Okada, A. Maruyama, M. Matsumoto, H. Yagita, and T. Seya.
    • Journal Title

      PLoS ONE

      Volume: 6 (4) Pages: e18833

  • [Journal Article] Raftlin is involved in the nucleocapture complex to induce poly(I : C)-mediated TLR3 activation2011

    • Author(s)
      Watanabe, A. M. Tatematsu, K. Saeki, S. Shibata, H. Shime, A. Yoshimura, C. Obuse, T. Seya, and M. Matsumoto.
    • Journal Title

      J . Biol. Chem

      Volume: 286 Pages: 10702-10711

  • [Journal Article] Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR22011

    • Author(s)
      Sawahata, R., H. Shime, S. Yamazaki, N. Inoue, T. Akazawa, Y. Fujimoto, K. Fukase, M. Matsumoto, and T. Seya.
    • Journal Title

      Microbes Infect

      Volume: 13(4) Pages: 350-358

  • [Journal Article] Natural killer cell activation secondary to innate pattern sensing2011

    • Author(s)
      Seya T. J. Kasamatsu, M. Azuma, H. shime, and M. Matsumoto.
    • Journal Title

      J . Innate Immun

      Volume: 3(3) Pages: 264-273

  • [Journal Article] Antiviral responses induced by the TLR3 pathway2011

    • Author(s)
      Matsumoto, M., H. Oshiumi, and T. Seya.
    • Journal Title

      Rev. Med. Virol

      Volume: 21 Pages: 67-77

  • [Journal Article] RNAウイルス感染に対する自然免疫応答2011

    • Author(s)
      押海裕之、松本美佐子、瀬谷司
    • Journal Title

      ウイルス、日本ウイルス学会誌

      Volume: 61 Pages: 153-162

  • [Journal Article] ワクチン増強剤としての抗がんRNAアジュバントの展望2011

    • Author(s)
      瀬谷司、松本美佐子
    • Journal Title

      細胞

      Volume: 43 (3) Pages: 20-23

  • [Journal Article] 自然免疫と癌治療2011

    • Author(s)
      瀬谷司、押海裕之、志馬寛明、松本美佐子
    • Journal Title

      実験医学(増刊)

      Volume: 29(2) Pages: 111-118

  • [Journal Article] 食細胞機能の増強2011

    • Author(s)
      松本美佐子
    • Journal Title

      補体への招待

      Pages: 79-87

  • [Presentation] Development of ideal adjuvant for cancer vaccine : Beyond the scope of current immunotherapy for cancer2014

    • Author(s)
      Tsukasa Seya and Misako Matsumoto
    • Organizer
      The 4th International Symposium on Carcinogenic Spiral. Infection, Immunity, and Cancer
    • Place of Presentation
      札幌(京王プラザホテル)
    • Year and Date
      2014-02-10
  • [Presentation] ヒトToll-like receptor 8のリガンド認識機構の解析2013

    • Author(s)
      石井朝子、舟見健児、立松恵、瀬谷司、松本美佐子
    • Organizer
      第36回日本分子生物学会学術集会
    • Place of Presentation
      兵庫
    • Year and Date
      20131203-06
  • [Presentation] Raftlin regulates Toll-like receptor 4-mediated signaling2013

    • Author(s)
      Megumi Tatematsu, Ryuji Yoshida, Kazuko Saeki, Tsukasa Seya, Misako Matsumoto
    • Organizer
      第36回日本分子生物学会学術集会
    • Place of Presentation
      兵庫
    • Year and Date
      20131203-06
  • [Presentation] TLR3 recognizes single-stranded RNA with incomplete stem structures2013

    • Author(s)
      Megumi Tatematsu, Fumiko Nishikawa, Tsukasa Seya and Misako Matsumoto
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      Milan, Italy
    • Year and Date
      20130822-27
  • [Presentation] 自然免疫レセプターTLR3によって認識されるRNA構造2013

    • Author(s)
      松本美佐子
    • Organizer
      第50回補体シンポジウム
    • Place of Presentation
      旭川
    • Year and Date
      2013-07-05
  • [Presentation] Role of Raftlin in Toll-Like Receptor 4-mediated Signaling2012

    • Author(s)
      Ryuji Yoshida, Megumi Tatematsu, Tsukasa Seya, Misako Matsumoto
    • Organizer
      第41日本免疫学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      20121205-07
  • [Presentation] Properties of viral single-stranded RNAs that harbor ability for emdosomal TLR3 targeting2012

    • Author(s)
      Megumi Tatematsu, Tsukasa Seya, and Misako Matsumoto
    • Organizer
      第41日本免疫学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      20121205-07
  • [Presentation] ウイルスゲノム由来の一本鎖RNAによるToll-like receptor 3活性化の解析2012

    • Author(s)
      立松恵、瀬谷司、松本美佐子
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      20121113-15
  • [Presentation] Toll-like receptor 3による核酸認識とシグナル伝達2012

    • Author(s)
      松本美佐子
    • Organizer
      第16回日本がん免疫学会総会
    • Place of Presentation
      札幌
    • Year and Date
      20120726-28
  • [Presentation] What immune responses are evoked by selective stimulation of the TLR3/TICAM-1 pathway in vaccination?2012

    • Author(s)
      Tsukasa Seya, Masahiro Azuma, Hiroaki Shime, Misako Matsumoto
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Ottawa, Canada
    • Year and Date
      2012-12-16
  • [Presentation] Toll-like receptor 3を活性化するRNA構造の同定2012

    • Author(s)
      立松恵、瀬谷司、松本美佐子
    • Organizer
      第49回日本生化学会北海道支部例会
    • Place of Presentation
      札幌
    • Year and Date
      2012-07-20
  • [Presentation] C-induced cross-priming and antitumor CTL depends on the TICAM-1 pathway in mouse Ag-presenting cells2011

    • Author(s)
      AZUMA Masahiro, EBIHARA Takashi, MATSUMOTO Misako, SEYA Tsukasa. PolyI
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Year and Date
      20111127-29
  • [Presentation] NC93B1 physically associates with human TLR8 and regulates TLR8-mediated signaling2011

    • Author(s)
      Megumi Tatematsu, Hiroki Itoh, Ayako Watanabe, Katsunori Iwano, Kenji Funami, Tsukasa Seya and Misako Matsumoto
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Year and Date
      20111127-29
  • [Presentation] Virus-derived single-stranded RNA with stable secondary structure extracellularly activates Toll-like receptor 32011

    • Author(s)
      Megumi Tatematsu, Tsukasa Seya, and Misako Matsumoto
    • Organizer
      IUMS 2011 Congress
    • Place of Presentation
      Sapporo, Japan
    • Year and Date
      20110911-16
  • [Book] Endosome Signaling Part B, Vol 535, Assessment of the Toll-like receptor 3 pathway in endosomal signaling2013

    • Author(s)
      Matsumoto M., K. Funami, M. Tatematsu, M. Azuma, and T. Seya., (Edited by P. Michael Conn. Academic Press, ELSEVIER INC)
    • Total Pages
      149-165
    • Publisher
      Methods Enzymol
  • [Book] Jesus Giraldo, editors : Oligomerization in Health and Disease, Vol 117, PMBTS, UK, Toll-IL-1-receptor-containing adaptor molecule-1 (TICAM-1), a signaling adaptor linking innate immunity to adaptive immunity2013

    • Author(s)
      Matsumoto, M., K. Funami, H. Oshiumi, and T. Seya.
    • Total Pages
      485-510
    • Publisher
      Academic Press

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Published: 2015-07-16   Modified: 2023-03-16  

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