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Immune regulation by chemokine-receptor associating molecule FROUNT

Research Project

Project/Area Number 17K15716
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionNippon Medical School (2019-2021)
Tokyo University of Science (2018)
The University of Tokyo (2017)

Principal Investigator

Etsuko Toda  日本医科大学, 医学部, 助教 (00589327)

Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsケモカイン受容体 / サイトカイン / マクロファージ / FROUNT / ケモカイン / 適応免疫応答 / 関節リウマチ
Outline of Final Research Achievements

The intracellular molecule FROUNT binds to the chemokine receptors CCR2 and CCR5, triggering macrophage migration to inflammatory sites. FROUNT has been shown to play an important role in the pathogenesis of inflammatory diseases through the regulation of macrophage migration and accumulation. However, the role of FROUNT in the regulation of adaptive immune responses is unknown. In this study, we analyzed the effect of FROUNT-deficiency on the responsiveness of macrophages to various stimuli. We found that FROUNT deficiency did not affect macrophage differentiation. However, FROUNT deficiency altered the cytokine production patterns of macrophages to various stimuli, suggesting its relevance to the regulation of adaptive immune responses.

Academic Significance and Societal Importance of the Research Achievements

マクロファージは炎症の引き金となって感染防御に働いたり、組織修復を促進するなど多様な働きで生体防御・維持に寄与する一方、炎症による組織傷害や、がん増生を助長するなど病態の悪化に働いてしまうことがある。そのため、マクロファージの機能を制御することによりがんや炎症性疾患を治療する試みが注目されている。本研究はマクロファージの動きを制御するケモカイン受容体会合分子FROUNTに着目して、マクロファージによる獲得免疫応答制御機構におけるFROUNTの新たな機能を明らかにし、マクロファージの動きと免疫応答の双方を制御可能な効果的ながん・炎症性疾患治療法につながることが期待される。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (22 results)

All 2022 2021 2020 2019 2018 2017 Other

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (11 results) (of which Int'l Joint Research: 4 results) Remarks (2 results)

  • [Journal Article] Disulfiram Produces Potent Anxiolytic-Like Effects Without Benzodiazepine Anxiolytics-Related Adverse Effects in Mice2022

    • Author(s)
      Saitoh Akiyoshi、Nagayama Yoshifumi、Yamada Daisuke、Makino Kosho、Yoshioka Toshinori、Yamanaka Nanami、Nakatani Momoka、Takahashi Yoshino、Yamazaki Mayuna、Shigemoto Chihiro、Ohashi Misaki、Okano Kotaro、Omata Tomoki、Toda Etsuko、Sano Yoshitake、Takahashi Hideyo、Matsushima Kouji、Terashima Yuya
    • Journal Title

      Frontiers in Pharmacology

      Volume: 13

    • DOI

      10.3389/fphar.2022.826783

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Uterine leiomyosarcomas with osteoclast-like giant cells associated with high expression of RUNX2 and RANKL2021

    • Author(s)
      Terasaki Mika、Terasaki Yasuhiro、Wakamatsu Kyoko、Kuwahara Naomi、Yoneyama Koichi、Kawase Rieko、Kurose Keisuke、Toda Etsuko、Endo Yoko、Kunugi Shinobu、Kajimoto Yusuke、Shimizu Akira
    • Journal Title

      Virchows Archiv

      Volume: 478 Issue: 5 Pages: 893-904

    • DOI

      10.1007/s00428-020-02996-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] マクロファージの動きを制御するFROUNTによるがん免疫応答の修飾作用2021

    • Author(s)
      遠田悦子、寺島裕也
    • Journal Title

      Medical Science Digest

      Volume: 47 Pages: 52-53

    • Related Report
      2020 Research-status Report
  • [Journal Article] アルコール依存症治療薬ジスルフィラムによるがん抑制効果の分子標的2021

    • Author(s)
      遠田悦子、寺島裕也
    • Journal Title

      糖尿病・内分泌代謝科

      Volume: 53 Pages: 37-44

    • NAID

      40022472572

    • Related Report
      2020 Research-status Report
  • [Journal Article] Targeting FROUNT with disulfiram suppresses macrophage accumulation and its tumor-promoting properties2020

    • Author(s)
      Yuya Terashima, Etsuko Toda, Kouji Matsushima et al.
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 1-16

    • DOI

      10.1038/s41467-020-14338-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] がん免疫応答に関わるサイトカイン・ケモカイン2019

    • Author(s)
      遠田悦子、寺島裕也、松島綱治
    • Journal Title

      実験医学増刊 がん免疫療法の個別化を支える新・腫瘍免疫学

      Volume: 37 Pages: 86-91

    • Related Report
      2019 Research-status Report
  • [Journal Article] 1H, 13C and 15N resonance assignments for a chemokine receptor-binding domain of FROUNT, a cytoplasmic regulator of chemotaxis2018

    • Author(s)
      Yoshinaga Sosuke、Ishida Norihito、Tsuji Tatsuichiro、Sonoda Akihiro、Yunoki Kaori、Takeda Mitsuhiro、Toda Etsuko、Terashima Yuya、Matsushima Kouji、Terasawa Hiroaki
    • Journal Title

      Biomolecular NMR Assignments

      Volume: 印刷中 Issue: 2 Pages: 259-262

    • DOI

      10.1007/s12104-018-9819-2

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficient identification of compounds suppressing protein precipitation via solvent screening using serial deletion mutants of the target protein2018

    • Author(s)
      Yunoki Kaori、Yoshinaga Sosuke、Takeda Mitsuhiro、Nagano Ryohei、Tsuchiya Yusuke、Sonoda Akihiro、Tsuji Tatsuichiro、Hirakane Makoto、Toda Etsuko、Terashima Yuya、Matsushima Kouji、Terasawa Hiroaki
    • Journal Title

      Genes to Cells

      Volume: 23 Issue: 2 Pages: 70-79

    • DOI

      10.1111/gtc.12554

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification and Preparation of a Novel Chemokine Receptor-Binding Domain in the Cytoplasmic Regulator FROUNT.2017

    • Author(s)
      Sonoda A, Yoshinaga S, Yunoki K, Ezaki S, Yano K, Takeda M, Toda E, Terashima Y, Matsushima K, Terasawa H.
    • Journal Title

      Mol Biotechnol

      Volume: 印刷中 Issue: 4-5 Pages: 141-150

    • DOI

      10.1007/s12033-017-0002-2

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] A cell migration-promoting molecule FROUNT regulates macrophage activation2021

    • Author(s)
      Etsuko Toda, Yuya Terashima and Kouji Matsushima
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ケモカイン受容体会合分子FROUNTのがん進展への関与と治療応用2020

    • Author(s)
      遠田 悦子、寺島 裕也、松島 綱治、清水 章
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] A chemokine signal amplifier FROUNT regulates tumor cell-mediated macrophage activation and migration to tumor sites2019

    • Author(s)
      Etsuko Toda, Yuya Terashima, Koji Matsushima
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] ケモカイン受容体シグナル促進分子FROUNT(フロント)の関節リウマチ病態への関与2019

    • Author(s)
      遠田悦子、寺島裕也、松島綱治
    • Organizer
      第18回分子予防環境医学研究会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] A molecular approach to block interaction between chemokine receptor and cytosolic regulator FROUNT for the control of monocyte/macrophage migration2019

    • Author(s)
      Etsuko Toda, Yuya Terashima, Kaori Esaki, Sosuke Yoshinaga, Hiroaki Terasawa and Kouji Matsushima
    • Organizer
      KeystoneSymposia
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Blocking tumor-promoting macrophages by interrupting the interaction of chemokine receptors and a cytoplasmic regulatory protein FROUNT2018

    • Author(s)
      Etsuko Toda, Yuya Terashima, Koji Matsushima
    • Organizer
      第45回内藤カンファレンス
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] A chemokine signal amplifier FROUNT promotes tumor progression by facilitating migration and activation of tumor-associated macrophages2018

    • Author(s)
      Etsuko Toda、Koji Matsushima
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 3.A therapeutic target site in chemokine receptors which is essential for binding with a cytoplasmic regulator FROUNT for regulating leukocyte chemotaxis2018

    • Author(s)
      Etsuko Toda, Yuya Terashima and Kouji Matsushima
    • Organizer
      Keystone symposia-Lymphocytes and their Roles in Cancer
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 5.A pivotal region for FROUNT-mediated chemotactic signaling that is shared by inflammatory chemokine receptors CCR2 and CCR52018

    • Author(s)
      Etsuko Toda, Yuya Terashima, Sosuke Yoshinaga, Hiroaki Terasawa and Kouji Matsushima
    • Organizer
      5th Annual Meeting of the International Cytokine and Interferon Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 7.ケモカイン受容体会合分子FROUNTの担癌状態における発現量変化とマクロファージ動態に及ぼす影響の解析2017

    • Author(s)
      遠田悦子、寺島裕也、松島綱治
    • Organizer
      第26回日本癌病態治療研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 8.単球・マクロファージの遊走促進分子FROUNTを標的としたがん微小環境制御2017

    • Author(s)
      遠田悦子、寺島裕也、板倉明司、奥村和弘、永瀬浩喜、松島綱治
    • Organizer
      第21回日本がん分子標的治療学会学術集会
    • Related Report
      2017 Research-status Report
  • [Remarks] 日本医科大学解析人体病理学教室ホームページ

    • URL

      https://pathology-nms.org/

    • Related Report
      2020 Research-status Report 2019 Research-status Report
  • [Remarks] 東京理科大学生命医科学研究所松島研究室ホームページ

    • URL

      https://k-matsushimalab.org/

    • Related Report
      2019 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2023-01-30  

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