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Role of lysosome-resident amino acid transporters in inflammatory response

Research Project

Project/Area Number 18K07056
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionNational Center for Global Health and Medicine

Principal Investigator

KOBAYASHI Toshihiko  国立研究開発法人国立国際医療研究センター, その他部局等, 副プロジェクト長 (40613203)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords炎症 / リソソーム / トランスポーター / アミノ酸トランスポーター / 炎症応答 / 免疫細胞 / 免疫 / 免疫疾患
Outline of Final Research Achievements

This research project was conducted to reveal the novel inflammatory signaling via a lysosome-resident amino acid transporter SLC15A3 and the molecular mechanism how this transporter contributes to the pathology of chronic inflammation. Throughout the period, we analyzed (1) the regulation mechanism of inflammation by SLC15A3, (2) identified the cell types that are positive for SLC15A3 during the inflammatory responses (3) searched the SLC15A3-associated molecules in order to understand the molecular machinery of SLC15A3-mediated inflammatory responses. As a result, we found out that SLC15A3 plays an important role in maintaining the pulmonary inflammation and symptom of diffuse alveolar hemorrhage, which was mostly mediated by inflammatory monocytes or neutrophils that express SLC15A3 gene at high level. We also identified several SLC15A3-associated molecules by research collaboration, and predicted the SLC15A3-mediated signaling pathways.

Academic Significance and Societal Importance of the Research Achievements

本研究では、リソソーム局在アミノ酸トランスポーターSLC15A3を介した新規炎症シグナルの制御機構、および慢性炎症疾患の病態制御における役割の解明を通じて、SLC15A3による新規炎症制御機構を明らかにすることを試みた。本研究成果の一部は既に学会等において公表済みであり、アミノ酸トランスポーターによる細胞内代謝変化を介した免疫応答の制御機構は、免疫学のみならず細胞生物学領域にも大きなインパクトと波及効果をもたらすことが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (8 results)

All 2021 2020 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Human SLC15A4 is crucial for TLR-mediated type I interferon production and mitochondrial integrity2021

    • Author(s)
      Kobayashi Toshihiko、Nguyen-Tien Dat、Ohshima Daisuke、Karyu Hitomi、Shimabukuro-Demoto Shiho、Yoshida-Sugitani Reiko、Toyama-Sorimachi Noriko
    • Journal Title

      International Immunology

      Volume: Online ahead of print Issue: 7 Pages: 399-406

    • DOI

      10.1093/intimm/dxab006

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Type I interferon limits mast-cell-mediated anaphylaxis by controlling secretory-granule homeostasis.2019

    • Author(s)
      Kobayashi T, Shimabukuro-Demoto S, Tsutsui H, Toyama-Sorimachi N
    • Journal Title

      PLoS Biology

      Volume: 17 Issue: 11 Pages: e3000530-e3000530

    • DOI

      10.1371/journal.pbio.3000530

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] A novel mechanisms of lung fibrosis mediated by an amino acid transporter2020

    • Author(s)
      Nguyen-Tien D, Kobayashi T, Toyama-Sorimachi N
    • Organizer
      Keystone Symposia, Fibrosis and tissue repair
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Unique role of an oligopeptide transporter SLC15A3 in the lung inflammation and resolution2019

    • Author(s)
      Kobayashi T, Nguyen-Tien Dat, Toyama-Sorimachi N
    • Organizer
      第48回日本免疫学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] SLC15A3 inhibits autophagy in macrophage and dendritic cells2019

    • Author(s)
      Nguyen-Tien D, Kobayashi T, Toyama-Sorimachi N
    • Organizer
      第48回日本免疫学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Controlling the innate immune responses by the lysosome-resident oligopeptide transporters.2019

    • Author(s)
      Kobayashi T, Toyama-Sorimachi N
    • Organizer
      9th FAOPS Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肺組織の炎症と修復におけるペプチドトランスポーターSLC15A3の役割2018

    • Author(s)
      小林俊彦、筒井英充、反町典子
    • Organizer
      第13回トランスポーター研究会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Regulation of allergic response by non-canonical type I interferon signaling.2018

    • Author(s)
      Kobayashi T, Tsutsui H, Toyama-Sorimachi N
    • Organizer
      6th Annual meeting of the International Cytokine and Interferon Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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