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Molecular basis underlying Toll-like receptor logistics

Research Project

Project/Area Number 25253032
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionThe University of Tokyo

Principal Investigator

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

Co-Investigator(Renkei-kenkyūsha) SAITOH Shin-Ichiroh  東京大学, 医科学研究所, 助教 (90361625)
Project Period (FY) 2013-10-21 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥43,940,000 (Direct Cost: ¥33,800,000、Indirect Cost: ¥10,140,000)
Fiscal Year 2015: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2014: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2013: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Keywords自然免疫 / Toll様受容体
Outline of Final Research Achievements

Toll-like receptors (TLRs) sense microbial products and induce defense responses. TLRs also respond to self derived products and causes inflammatory diseases. The present study focused on the molecular mechanism regulating TLR responses. TLR trafficking in endolysosomes controls TLR responses. The roles of small GTPases in TLR trafficking was studied. We also studied the roles of: proteolytic processing of the extracellular domain of TLR9 and TLR3 in their responses; and DNase II in DNA processing for TLR9 responses.These results show that TLR responses are regulated at a variety of processes.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (21 results)

All 2016 2015 2014 2013

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Acknowledgement Compliant: 6 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 10 results)

  • [Journal Article] Type I IFN Contributes to the Phenotype of Unc93b1D34A/D34A Mice by Regulating TLR7 Expression in B Cells and Dendritic Cells2016

    • Author(s)
      Fukui R, Kanno A, Miyake K
    • Journal Title

      J Immunol

      Volume: 196 Issue: 1 Pages: 416-427

    • DOI

      10.4049/jimmunol.1500071

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Toll-like receptor 8 senses degradation products of single-stranded RNA.2015

    • Author(s)
      Tanji H, Ohto U, Shibata T, Taoka M, Yamauchi Y, Isobe T, Miyake K,
    • Journal Title

      Nat Struct Mol Biol.

      Volume: 22 Issue: 2 Pages: 109-115

    • DOI

      10.1038/nsmb.2943

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cell-intrinsic expression of TLR9 in autoreactive B cells constrains BCR/TLR7-dependent responses.2015

    • Author(s)
      Nundel K, Green NM, Shaffer AL, Moody KL, Busto P, Eilat D, Miyake K, Oropallo MA, Cancro MP, Marshak-Rothstein A
    • Journal Title

      J Immunol.

      Volume: 194 Issue: 6 Pages: 2504-2512

    • DOI

      10.4049/jimmunol.1402425

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9.2015

    • Author(s)
      Ohto, U., Shibata, T., Tanji, H., Krayukhina, E., Uchiyama, S., Miyake, K., and Shimizu, T.
    • Journal Title

      Nature

      Volume: 520 Issue: 7549 Pages: 702-705

    • DOI

      10.1038/nature14138

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] DNase II-dependent DNA digestion is required for DNA sensing by TLR92015

    • Author(s)
      Chan MP, Onji M, Fukui R, Kawane K, Shibata T, Saitoh SI, Ohto U, Shimizu T, Barber GN, *Miyake K
    • Journal Title

      Nat Commun

      Volume: 6 Issue: 1 Pages: 5853-5853

    • DOI

      10.1038/ncomms6853

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases2015

    • Author(s)
      Kanno A, Tanimura N, Ishizaki M, Ohko K, Motoi Y, Onji M, Fukui R, Shimozato T, Yamamoto K, Shibata T, Sano S, Sugahara-Tobinai A, Takai T, Ohto U, Shimizu T, Saitoh S, Miyake K.
    • Journal Title

      Nature Communications

      Volume: 6 Issue: 1 Pages: 6119-6119

    • DOI

      10.1038/ncomms7119

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mucolipin 1 positively regulates TLR7 responses in dendritic cells by facilitating RNA transportation to lysosomes2015

    • Author(s)
      Li X, Saitoh S, Shibata T, Tanimura N, Fukui R, Miyake K.
    • Journal Title

      International immunology

      Volume: 27 Issue: 2 Pages: 83-94

    • DOI

      10.1093/intimm/dxu086

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lipopeptides are signaled by Toll-like receptor 1, 2, and 6 in endolysosomes2014

    • Author(s)
      Motoi Y, Shibata T, Takahashi K, Kanno A, Murakami Y, Xiaobing L, Kasahara T, *Miyake K
    • Journal Title

      Int Immunol

      Volume: 26 Issue: 10 Pages: 563-573

    • DOI

      10.1093/intimm/dxu054

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Roles of the Cleaved N-Terminal TLR3 Fragment and Cell Surface TLR3 in Double-Stranded RNA Sensing2014

    • Author(s)
      Murakami Y, Fukui R, Motoi Y, Kanno A, Shibata T, Tanimura N, Saitoh SI, *Miyake K
    • Journal Title

      J Immunol

      Volume: 193 Pages: 5208-5217

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [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 Issue: 1 Pages: 1949-1949

    • DOI

      10.1038/ncomms2949

    • NAID

      120005359107

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endocytosis-free DNA sensing by cell surface TLR9 in neutrophils: Rapid defense with autoimmune risks2013

    • Author(s)
      Miyake K, Onji M
    • Journal Title

      Eur J Immunol

      Volume: 43 Issue: 8 Pages: 2006-2009

    • DOI

      10.1002/eji.201343882

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Toll様受容体によるRNA認識におけるRNAプロセシングの役割2015

    • Author(s)
      三宅健介
    • Organizer
      第88回日本生化学会年会
    • Place of Presentation
      神戸ポートアイランド (兵庫県 神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Innate Immune Response to nucleic acids in inflammatory disorders2015

    • Author(s)
      Kensuke Miyake
    • Organizer
      the 63rd annual meeting of the Japanese Association of Dental Research
    • Place of Presentation
      福岡国際会議場(福岡県 福岡市)
    • Year and Date
      2015-10-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The role of Nucleic acid processing in nucleic acid sensing by Toll-like receptors2015

    • Author(s)
      Kensuke Miyake
    • Organizer
      Toll 2015
    • Place of Presentation
      Marbella, Spain
    • Year and Date
      2015-09-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Nucleic Acid recognition by Toll-like receptors2015

    • Author(s)
      Kensuke Miyake
    • Organizer
      National Institute of Chemistry meeting in slovenia
    • Place of Presentation
      Ljubjana, Slovenia
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Nucleic acid recognition by Toll-like receptors2015

    • Author(s)
      Kensuke Miyake
    • Organizer
      Innate Immunity Day, University of Massachusetts
    • Place of Presentation
      Worcester, USA
    • Year and Date
      2015-05-20
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Toll様受容体の活性制御機構とその破綻2014

    • Author(s)
      三宅健介
    • Organizer
      第9回臨床ストレス応答学会
    • Place of Presentation
      岡山大学鹿田キャンパス
    • Year and Date
      2014-11-01 – 2014-11-02
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Mechanisms regulating nucleic acid sensing Toll-like receptors2014

    • Author(s)
      三宅健介
    • Organizer
      第13回国際エンドトキシン自然免疫学会
    • Place of Presentation
      ソルトレークシティー  米国
    • Year and Date
      2014-10-23 – 2014-10-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Toll様受容体による核酸認識の制御機構2014

    • Author(s)
      三宅健介
    • Organizer
      日本生化学会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Toll様受容体の活性制御機構とその破綻2014

    • Author(s)
      三宅健介
    • Organizer
      日本乾癬学会
    • Place of Presentation
      高知市文化プラザ カルポート
    • Year and Date
      2014-09-19 – 2014-09-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Mechanisms regulating Nucleic acid-sensing Toll-like receptors2014

    • Author(s)
      三宅健介
    • Organizer
      日本リウマチ学会
    • Place of Presentation
      新高輪プリンスホテル
    • Year and Date
      2014-04-24 – 2014-04-25
    • Related Report
      2014 Annual Research Report
    • Invited

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Published: 2013-10-24   Modified: 2019-07-29  

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