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The regulation of cytokine production by phospholipid on MVB

Research Project

Project/Area Number 26860189
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Research InstitutionOsaka University

Principal Investigator

Sasai Miwa  大阪大学, 微生物病研究所, 助教 (30631551)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsTLR / IFN / trafficking / サイトカイン産生 / 感染制御 / 小胞輸送
Outline of Final Research Achievements

Recent studies indicate that signals from these TLRs bifurcate at the level of distinct endosomal compartments to mediate the induction of cytokine and type I interferon (IFN) genes. TLR9 mediates signals for cytokines from VAMP3+ endosome, and induces IFN genes from LAMP2+ endosome. Phosphoinositides mark distinct subcellular membranes and control membrane trafficking. However, their role in TLR trafficking and signaling remains unclear. Here, we examined the role of phosphatidylinositol 3P 5-kinase, PIKfyve, in TLR trafficking and signaling. We demonstrate that inhibition of PIKfyve activity preferentially blocks TLR9 signaling for type I IFN induction in pDCs. By confocal microscopy, we show that trafficking of both TLR9 and CpG to the LAMP1+ compartment is blocked by PIKfyve inhibitor treatment. These data indicate that PIKfyve provides critical phosphoinositides necessary for the formation of endosome from which TLR9 signals to induce type I IFNs.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (14 results)

All 2015 2014 Other

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

  • [Journal Article] Toll-like receptor 9 trafficking and signaling for type I interferons requires PIKfyve activity.2015

    • Author(s)
      Hayashi K, Sasai M, Iwasaki A
    • Journal Title

      International Immunology

      Volume: 9 Issue: 9 Pages: 435-445

    • DOI

      10.1093/intimm/dxv021

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Selective and strain-specific NFAT4 activation by the Toxoplasma gondii polymorphic dense granule protein GRA62014

    • Author(s)
      Ji Su Ma, Miwa Sasai, Jun Ohshima, Youngae Lee, Hironori Bando, Kiyoshi Takeda, and Masahiro Yamamoto
    • Journal Title

      The Journal of Experimental Medicine

      Volume: 211 Issue: 10 Pages: 2013-2032

    • DOI

      10.1084/jem.20131272

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Role of Mouse and Human Autophagy Proteins in IFN-γ-Induced Cell-Autonomous Responses against Thxoplasma gondii2014

    • Author(s)
      Jun Ohshima, Youngae Lee, Miwa Sasai, Tatsuya Saitoh, Ji Su Ma, Naganori Kamiyama, Yoshiharu Matsuura, Suh Pann-Ghill, Mikako Hayashi, Shigeyuki Ebisu, Kiyoshi Takeda, Shizuo Akira, and Masahiro Yamamoto.
    • Journal Title

      The Journal of Immunology

      Volume: 192(7) Issue: 7 Pages: 3328-35

    • DOI

      10.4049/jimmunol.1302822

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] RabGDIα is a negative regulator of interferon-γ-inducible GTPase-dependent cell-autonomous immunity to Toxoplasma gondii2015

    • Author(s)
      Miwa Sasai, Jun Ohshima, Ji Su Ma, Youngae Lee, Kiyoshi Takeda, Masahiro Yamamoto
    • Organizer
      The 44th Annual Meeting of The Japanese Society for Immunology
    • Place of Presentation
      札幌
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] トキソプラズマ原虫の多型濃縮顆粒タンパク質GRA6による選択的NFAT4の活性化について.2015

    • Author(s)
      馬知秀, 笹井美和, 大嶋淳, Lee Youngae, 伴戸寛徳, 竹田潔, 山本雅裕.
    • Organizer
      第84回日本寄生虫学会大会
    • Place of Presentation
      東京/杏林大学三鷹キャンパス
    • Year and Date
      2015-03-21 – 2015-03-22
    • Related Report
      2014 Research-status Report
  • [Presentation] 肝臓期マラリア原虫を標的とした新規抗マラリア薬の開発.2015

    • Author(s)
      伴戸寛徳, 笹井美和, 馬知秀, 大嶋淳, Lee Youngae, 山本雅裕.
    • Organizer
      第84回日本寄生虫学会大会
    • Place of Presentation
      東京/杏林大学三鷹キャンパス
    • Year and Date
      2015-03-21 – 2015-03-22
    • Related Report
      2014 Research-status Report
  • [Presentation] Selective and strain-specific NFAT4 activation by the Toxoplasma gondii polymorphic dense granule protein GRA6.2015

    • Author(s)
      馬知秀, 笹井美和, 大嶋淳, Lee Youngae, 伴戸寛徳, 竹田潔, 山本雅裕
    • Organizer
      第8回 寄生虫感染免疫研究会
    • Place of Presentation
      大阪/大阪大学
    • Year and Date
      2015-02-27 – 2015-02-28
    • Related Report
      2014 Research-status Report
  • [Presentation] RabGDIα is a negative regulator of interferon-γ-inducible GTPase-dependent cell-autonomous host defense against Toxoplasma gondii.2015

    • Author(s)
      大嶋淳, 笹井美和, 馬知秀, Lee Youngae, 伴戸寛徳, 山本雅裕.
    • Organizer
      第8回 寄生虫感染免疫研究会
    • Place of Presentation
      大阪/大阪大学
    • Year and Date
      2015-02-27 – 2015-02-28
    • Related Report
      2014 Research-status Report
  • [Presentation] Toxoplasma gondii GRA6 selectively activates NFAT4 to induce chemokine CXCL2 and CCL2.2014

    • Author(s)
      笹井美和, 馬知秀, 大嶋淳, Lee Youngae, 竹田潔, 山本雅裕.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都/国際会議場
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Role of mouse autophagy proteins in IFN-γ-mediated cell-autonomous responses against Toxoplasma gondii.2014

    • Author(s)
      大嶋淳, 笹井美和, 馬知秀, Lee Youngae, 竹田潔, 山本雅裕.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都/国際会議場
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Human ATG16L1 and GBPs are dispensable for IFN-γ–dependent anti–Toxoplasma gondii responses.2014

    • Author(s)
      Lee Youngae, 大嶋淳, 笹井美和, 馬知秀, 山本雅裕.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都/国際会議場
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Research-status Report
  • [Presentation] インターフェロン-γ誘導性GTPaseによるトキソプラズマ原虫殺傷機構について2014

    • Author(s)
      山本雅裕、大嶋淳、Lee Youngae、笹井美和.
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都/国際会議場
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] Activation of host NFAT by a Toxoplasma gondii polymorphic dense granule protein plays an important role in virulence mediated by the local infection.2014

    • Author(s)
      山本雅裕, 馬知秀, 大嶋淳, 笹井美和.
    • Organizer
      18th Annual Woods Hole ImmunoParasitology Conference.
    • Place of Presentation
      米国/マサチューセッツ州
    • Year and Date
      2014-04-27 – 2014-04-30
    • Related Report
      2014 Research-status Report
  • [Remarks] 感染病態分野 ホームページ

    • URL

      http://www.biken.osaka-u.ac.jp/lab/immpara/

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2017-05-10  

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