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2013 Fiscal Year Final Research Report

Toll like receptors; their endogenous ligands and mechanism regulating their activities

Planned Research

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Project AreaHomeostatic inflammation: Molecular basis and dysregulation
Project/Area Number 21117002
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

MIYAKE Kensuke  東京大学, 医科学研究所, 教授 (60229812)

Co-Investigator(Kenkyū-buntansha) OHTO Umeharu  東京大学, 薬学研究科, 助教 (90451856)
NAKANISHI Hiroki  秋田大学, 生体情報研究センター, 助教 (10466740)
Co-Investigator(Renkei-kenkyūsha) TAKAMURA Sachiko  東京大学, 医科学研究所, 助教 (00325599)
SITOH Shin-ichiroh  東京大学, 医科学研究所, 助教 (90361625)
Project Period (FY) 2009-07-23 – 2014-03-31
KeywordsToll様受容体
Research Abstract

Toll-like receptors (TLR) sense not only microbial products, but also self-derived endogenous products. We here searched endogenous ligands such as lipids and nucleic acids. We succeeded in solving the structure of TLR8. The structure predicts endogenous ligands to TLR8. Those ligands were studied by in vitro functional analyses. We also studied mechanisms regulating TLRs in the steady state. Unc93B1 controls TLR trafficking. We have found that Unc93B1 also has a role in regulating TLR7 responses in the steady state. These results suggest that TLRs steadily respond to endogenous ligands and their activities are tightly regulated.

  • Research Products

    (23 results)

All 2014 2013 2012 2011 2009 Other 0

All Journal Article (10 results) Presentation (11 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] UNC93B1 is essential for the plasma membrane localization and signaling of Toll-like receptor 52014

    • Author(s)
      Huh JW, Shibata T, Hwang M, Kwon EH, Jang MS, Fukui R, Kanno K, Jung DJ, Jang MH, Miyake K, and Kim YM
    • Journal Title

      Proc. Natl. Acad. Sci. USA

    • DOI

      10.1073/pnas.1322838111

  • [Journal Article] The attenuated inflammation of MPL is due to the lack of CD14-dependent tight dimerization of TLR4/MD2 complex at the plasma membrane2013

    • Author(s)
      Tanimura N, Saitoh S, Ohto U, Akashi-Takamura A, Fujimoto Y, Fukase K, Shimizu T, Miyake K
    • Journal Title

      Int. Immunol.

    • DOI

      10.1093/intimm/dxt071

  • [Journal Article] An essential role for the N-terminal fragment of Toll-like receptor 9 in DNA sensing2013

    • Author(s)
      Onji M, Kanno A, Saitoh S, Fukui R, Motoi Y, Shibata T, Matsumoto F, Lamichhane A, Sato S, Kiyono H, Yamamoto K, Miyake K
    • Journal Title

      Nat. Commun.

      Volume: 4 Pages: 1949

    • DOI

      10.1038/ncomms2949

  • [Journal Article] Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands2013

    • Author(s)
      Tanji H, Ohto U, Shibata T, Miyake K, Shimizu T
    • Journal Title

      Science

      Volume: 339 Pages: 1426-1429

    • DOI

      10.1126/science.1229159

  • [Journal Article] Human TLR4 polymorphism D299G/T399I alters TLR4/MD-2 conformation and response to a weak ligand monophosphoryl lipid A2013

    • Author(s)
      Yamakawa N, Ohto U, Akashi-Takamura S, Takahashi K, Saitoh SI, Tanimura N, Suganami T, Ogawa Y, Shibata T, Shimizu T, Miyake K
    • Journal Title

      Int Immunol.

      Volume: 25 Pages: 45-52

  • [Journal Article] PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells2012

    • Author(s)
      Shibata T, Takemura N, Motoi Y, Goto Y, Karuppuchamy T, Izawa K, Li X, Akashi-Takamura S, Tanimura N, Kunisawa J, Kiyono H, Akira S, Kitamura T, Kitaura J, Uematsu S, Miyake K
    • Journal Title

      Int Immunol.

      Volume: 24 Pages: 613-623

    • DOI

      10.1093/intimm/dxs068

  • [Journal Article] Structural analyses of human Toll-like receptor polymorphisms D299G and T399I2012

    • Author(s)
      Ohto U, Yamakawa N, Akashi-Takamura S, Miyake K, Shimizu T
    • Journal Title

      J Biol Chem.

      Volume: 287 Pages: 40611-40617

    • DOI

      10.1074/jbc.M112.404608

  • [Journal Article] Structural basis of species-specific endotoxin sensing by innate immune receptor TLR4/MD-22012

    • Author(s)
      Ohto U, Fukase K, Miyake K, Shimizu T
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 109 Pages: 7421-7426

    • DOI

      10.1073/pnas.1201193109

  • [Journal Article] Unc93B1 restricts systemic lethal inflammation by orchestrating TLR7 and TLR9-trafficking2011

    • Author(s)
      Fukui R, Saitoh S-I, Kanno A, Onji M, Shibata T, Ito A, Onji M, Matsumoto M, Akira S, Yoshida N, Miyake K
    • Journal Title

      Immunity

      Volume: 35 Pages: 69-81

  • [Journal Article] Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic cells towards DNA-but against RNA-sensing2009

    • Author(s)
      Fukui R, Saitoh S-I, Matsumoto F, Kozuka-Hara H, Oyama M, Tabeta K, Beutler B, and Miyake K
    • Journal Title

      J. Exp. Med.

      Volume: 206 Pages: 1339-1350

  • [Presentation] Nucleic acid-sensing Toll-like receptors : their recognition and regulation2013

    • Organizer
      The 21th international symposium of macrophage molecular and cellular biology (MMCB)2013
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      20130520-21
  • [Presentation] TLR logistics by Unc93B1 as a mechanism regulating autoimmunity2013

    • Organizer
      American Association of Immunologists (AAI) annual meeting 2013
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      20130503-07
  • [Presentation] Toll-like receptor logistics by Unc93B12012

    • Organizer
      Symposium"Homeostatic Inflammation against self-derived products" at The 85th Annual meeting of the Japanese Biochemical Society
    • Place of Presentation
      Fukuoka
    • Year and Date
      2012-12-15
  • [Presentation] Toll-like receptor logistics by Unc93B12012

    • Organizer
      Symposium in The biennial meeting of International endotoxin and innate immunity society
    • Place of Presentation
      Tokyo
    • Year and Date
      2012-10-24
  • [Presentation] Toll-like receptor logistics by Unc93B1 as a mechanism regulating autoimmunity2012

    • Organizer
      French-Japanese Meeting "Immune defenses in humans and model organisms
    • Place of Presentation
      Embassy of France in Japan
    • Year and Date
      2012-09-21
  • [Presentation] Toll-like receptor 7 in plasmacytoid DCs as a target for enhancing anti-tumor immunity2012

    • Organizer
      The 71st Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Sapporo
    • Year and Date
      2012-09-20
  • [Presentation] Toll-like receptor logistics by Unc93B12012

    • Organizer
      The 11th Awaji international forum on infection and immunity
    • Place of Presentation
      Awaji
    • Year and Date
      2012-09-12
  • [Presentation] TLR logistics by Unc93B1 as a mechanism regulating autoimmunity

    • Organizer
      France-Japan joint forum, Frontiers in Innate Immunity
    • Place of Presentation
      Univ. Strasbourg, Strasbourg, France
    • Year and Date
      00000606-07
  • [Presentation] Toll-like receptor logistics as a mechanism regulating autoimmunity

    • Organizer
      The 5th East Asian Group of Rheumatology
    • Place of Presentation
      Seoul, South Korea
    • Year and Date
      00000531-0601
  • [Presentation] Nucleic acid-sensing Toll-like receptors : their recognition and regulation0

    • Organizer
      The 86th annual meeting of the Japanese Society of Biochemical Society
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      00000913
  • [Presentation] Mechanisms Regulating Nucleic Acid Sensing Toll-like Receptors0

    • Organizer
      The 58th annual meeting of Japanese College of Rheumatology
    • Place of Presentation
      International symposium, Tokyo, Japan
    • Year and Date
      00000424
  • [Remarks]

    • URL

      http://www.shizen-enshow.jp/

  • [Patent(Industrial Property Rights)] 炎症性疾患の予防又は治療剤2013

    • Inventor(s)
      三宅健介、菅野敦夫、恩地正浩、本井祐二
    • Industrial Property Rights Holder
      東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      特願 2013-089575
    • Filing Date
      2013-04-22

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Published: 2015-06-25  

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