• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

自然免疫応答と脂質代謝の連携分子基盤の解明

Publicly Offered Research

Project AreaQuality of lipids in biological systems
Project/Area Number 18H04666
Research Category

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

Allocation TypeSingle-year Grants
Research InstitutionThe University of Tokyo

Principal Investigator

三宅 健介  東京大学, 医科学研究所, 教授 (60229812)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
KeywordsToll様受容体 / 自然免疫 / Toll-like receptor
Outline of Annual Research Achievements

代謝系と免疫系は密接に連携しているが、その連携において、代謝センサーmammalian target of rapamycin (mTOR)と自然免疫センサーとの連携の役割が明らかになりつつある。mTORはmTORC1、mTORC2という2つの複合体を形成する。mTORC1はリソソームに局在するアミノ酸のセンサーであると同時に、Toll-like Receptor (TLR)によるI型インターフェロン(Interferon, IFN)産生を誘導するシグナル伝達分子としても機能する。一方、mTORC2については、代謝センサーとしての役割さえも不明である。我々は既に、mTORC2が2重鎖RNAセンサーTLR3のマスター制御因子であるという結果を得ている。本研究において、mTORC2の代謝センサーとしての機能を検討するために、TLR3の応答と脂質代謝系との関係について解析を進めた。脂肪酸の合成に関与する遺伝子を欠損させると、TLR3によるNF-kBの活性化が低下することが分かった。この結果は、TLR3の応答と脂質代謝が密接に連関している可能性を示唆している。そこでその関係におけるmTORC1、mTORC2の役割について検討した。脂質非存在下でのTLR3の応答を検討したところ、TLR3のすべての応答が欠損しているという結果を得た。TLR3の応答すべてが脂質代謝に依存していることを考慮すると、mTORC1だけでは説明できない。我々はすでにmTORC2が直接TLR3に会合し、TLR3のすべての応答に関与していることを報告している。したがって、mTORC2が脂質代謝のTLR3応答に及ぼす影響に関与している可能性が示された。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (13 results)

All 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (9 results) (of which Int'l Joint Research: 8 results,  Invited: 9 results)

  • [Journal Article] Cytidine deaminase enables Toll-like receptor 8 activation by cytidine or its analogs.2019

    • Author(s)
      Furusho K, Shibata T, Sato R, Fukui R, Motoi Y, Zhang Y, Saitoh SI, Ichinohe T, Moriyama M, Nakamura S, Miyake, K.
    • Journal Title

      International immunology.

      Volume: 31 Issue: 3 Pages: 167-173

    • DOI

      10.1093/intimm/dxy075

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endolysosomal compartments as platforms for orchestrating innate immune and metabolic sensors2019

    • Author(s)
      Miyake Kensuke、Saitoh Shin‐ichiroh、Sato Ryota、Shibata Takuma、Fukui Ryutaro、Murakami Yusuke
    • Journal Title

      Journal of Leukocyte Biology

      Volume: 106 Issue: 4 Pages: 853-862

    • DOI

      10.1002/jlb.mr0119-020r

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis.2018

    • Author(s)
      Sato R, Kato A, Chimura T, Saitoh SI, Shibata T, Murakami Y, Fukui R, Liu K, Zhang Y, Arii J, Sun-Wada GH, Wada Y, Ikenoue T, Barber GN, Manabe T, Kawaguchi Y, Miyake K.
    • Journal Title

      Nat Immunol.

      Volume: 19 Issue: 10 Pages: 1071-1082

    • DOI

      10.1038/s41590-018-0203-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mechanisms controlling nucleic acid-sensing Toll-like receptors2018

    • Author(s)
      Miyake Kensuke、Shibata Takuma、Ohto Umeharu、Shimizu Toshiyuki、Saitoh Shin-Ichiroh、Fukui Ryutaro、Murakami Yusuke
    • Journal Title

      International Immunology

      Volume: 30 Issue: 2 Pages: 43-51

    • DOI

      10.1093/intimm/dxy016

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Mechanisms Controlling Innate Immune Responses to Nucleic Acids2019

    • Author(s)
      Kensuke Miyake
    • Organizer
      The 3rd annual Chiba-UCSD symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanisms Controlling Innate Immune Responses to Nucleic Acids2019

    • Author(s)
      Kensuke Miyake
    • Organizer
      5th workshop in biosciences, International Alliance of Research Internship (IARI) 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanisms Controlling Innate Immune Responses to Nucleic Acids2019

    • Author(s)
      Kensuke Miyake
    • Organizer
      The 26th international symposium on molecular cell biology of macrophages (MMCB2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanisms Controlling Innate Immune Responses to Nucleic Acids2019

    • Author(s)
      Kensuke Miyake
    • Organizer
      52nd annual meeting of the society for leukocyte biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 核酸特異的Toll様受容体と自己免疫疾患2019

    • Author(s)
      三宅 健介
    • Organizer
      第47回日本臨床免疫学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Mechanisms Controlling Innate Immune Responses to Nucleic Acids2018

    • Author(s)
      Kensuke Miyake
    • Organizer
      International Union of Biochemistry and Molecular Biology 2018 (IUBMB2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanisms Controlling Innate Immune Responses to Nucleic Acids2018

    • Author(s)
      Kensuke Miyake
    • Organizer
      51st annual meeting of the society for leukocyte biology and 15th biennial meeting of the international endotoxin and innate immunity society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanisms Controlling Innate Immune Responses to Nucleic Acids2018

    • Author(s)
      Kensuke Miyake
    • Organizer
      The 9th Asian congress of pediatric infectious diseases
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanisms Controlling Innate Immune Responses to Nucleic Acids2018

    • Author(s)
      Kensuke Miyake
    • Organizer
      The 47th annual meeting of the Japanese society for immunology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited

URL: 

Published: 2018-04-23   Modified: 2021-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi