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

Analysis of the protein acetylation that regulates intracellular signal transduction in T cells

Research Project

Project/Area Number 19K07613
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49070:Immunology-related
Research InstitutionToho University

Principal Investigator

Motonari Kondo  東邦大学, 医学部, 教授 (20594344)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords翻訳後修飾 / アセチル化 / T細胞機能 / 情報伝達 / T細胞受容体 / T細胞情報伝達 / 分子修飾 / T細胞 / タンパク質のアセチル化
Outline of Research at the Start

申請者はリンパ球をモデルにした解析で、核外へ輸送されたアセチル化酵素CBPが細胞質で基質タンパク質をアセチル化すること、このアセチル化が特定の情報伝達経路を調節し細胞機能を制御することを報告してきた。細胞質でのアセチル化が細胞の機能や運命を決定するといった独自の仮説を検証していくことが本研究の計画目標である。

先行研究でT細胞受容体下流でJNK経路の構成分子のアセチル化を検出したことから、この伝達経路を優先して解析する。アセチル化による調節機構を明らかにするため、CBPの基質を探索する。細胞質でのアセチル化の生体内における生理的意義を調べるため、細胞質でCBPを発現するマウスを作製する。

Outline of Final Research Achievements

T cells play critical role in immune system. Their role is closely related to the intracellular signal transduction. Protein phosphorylation is critical for the regulation of signal transduction activity. In this study, We demonstrated other post-translational modification such as protein acetylation regulate T cell function. Acetyltransferase CBP acetylates MAP kinase-kinase MKK4 after T cell receptor (TCR) stimulation. Activation JNK and AP-1, downstream molecules of MKK4, were prevented under the acetylated MKK4 condition. Cytokine production from T cell after TCR cross-link was also attenuated in the presence of acetylated MKK4. These results provide new insight in the role of acetylation in T cell function.

Academic Significance and Societal Importance of the Research Achievements

アセチル化はタンパク質の翻訳後修飾の1つで核内のヒストンを修飾するものとして古くから知られている。本研究ではアセチル化の新しい側面として、核内ではなく細胞質での意義について解析した。T細胞をモデルにして、細胞増殖やサイトカイン産生等のT細胞活性が情報伝達分子のアセチル化によって制御されている事を示した。しかしながらアセチル化の制御機構のについては未解のまま残されている。分子機構などの解析に関わる新しい研究分野の発展が期待される。また、T細胞は自己免疫疾患やガンなどの多岐の疾患に関与している。この分野に関するの知見を基にした医療面の開拓も期待でき、学術性と社会性の両面への貢献が予想される。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (27 results)

All 2022 2021 2020 2019

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (23 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Increased Indoleamine 2,3-Dioxygenase Levels at the Onset of Sjogren’s Syndrome in SATB1-Conditional Knockout Mice2021

    • Author(s)
      Tanaka Yuriko、Onozato Mayu、Mikami Tetuo、Kohwi-Shigematsu Terumi、Fukushima Takeshi、Kondo Motonari
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 18 Pages: 10125-10125

    • DOI

      10.3390/ijms221810125

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SATB1-dependent mitochondrial ROS production controls TCR signaling in CD4 T cells2021

    • Author(s)
      Kuwabara Taku、Ishikawa Fumio、Ikeda Masataka、Ide Tomomi、Kohwi-Shigematsu Terumi、Tanaka Yuriko、Kondo Motonari
    • Journal Title

      Life Science Alliance

      Volume: 4 Issue: 11 Pages: e202101093-e202101093

    • DOI

      10.26508/lsa.202101093

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High CD4 T cell/B cell ratio in the rapanasal sinus mucosa of patients with eosinophilic chronic rhiosinusktis.2020

    • Author(s)
      Akiko Inoue, Yuriko Tanaka, Shinya Ohira, Kentaro Matsuura, Motonari Kondo, Kota Wada
    • Journal Title

      International archives of Otorhinolaryngology

      Volume: 24 Pages: 1-5

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] シェーグレン症候群疾患モデルマウスにおけるB細胞活性化機構の解析2022

    • Author(s)
      田中ゆり子, 井上彰子, 近藤元就
    • Organizer
      第30回日本シェーグレン症候群学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] T細胞活性調節におけるミトコンドリアの役割解析2022

    • Author(s)
      桑原卓、近藤元就
    • Organizer
      Kyoto T Cell Conference
    • Related Report
      2022 Annual Research Report
  • [Presentation] SATB1-dependent mitochondrial ROS production controls TCR signaling in CD4 T cells.2022

    • Author(s)
      Taku Kuwabara, Marii Ise, Taku Naito, Yuriko Tanaka, Motonari Kondo
    • Organizer
      The 51st Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2022 Annual Research Report
  • [Presentation] Functional analyses of pathogenic T cells in autoimmune prone mice.2022

    • Author(s)
      Yuriko Tanaka, Akiko Inoue, Taku Naito, Taku Kuwabara, Marii Ise, Terumi Kohwi-Shigematsu, Motonari Kondo
    • Organizer
      The 51st Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2022 Annual Research Report
  • [Presentation] IL-7 regulates the expression of CD69 and CD103 on TRM cells in skin.2022

    • Author(s)
      Marii Ise, Taku Kuwabara, Yuriko Tanaka, Taku Naito, Motonari Kondo
    • Organizer
      The 51st Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2022 Annual Research Report
  • [Presentation] 自己免疫疾患モデルマウス病原性T細胞による組織障害メカニズムの解析2021

    • Author(s)
      田中ゆり子、井上彰子、近藤元就
    • Organizer
      Kyoto T cell conference 第30回学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] シェーグレン症候群疾患モデルマウス病原性T細胞による唾液腺組織障害機構の解析2021

    • Author(s)
      田中ゆり子、井上彰子、近藤元就
    • Organizer
      第29回 日本シェーグレン症候群学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] An early serum marker for Sjogren's syndrome in SATB1 deficient mice.2021

    • Author(s)
      Yuriko Tanaka, Akiko Inoue, Taku Kuwabara, Taku Naito, Marii Ise, Motonari Kondo
    • Organizer
      The 50th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2021 Research-status Report
  • [Presentation] Satb1 regulates thymocyte trafficking after positive selection.2021

    • Author(s)
      Taku Naito, Yuriko Tanaka, Taku Kuwabara, Marii Ise, Motonari Kondo
    • Organizer
      The 50th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2021 Research-status Report
  • [Presentation] アセチル化によるIL-2受容体シグナルの制御2021

    • Author(s)
      桑原卓、近藤元就
    • Organizer
      日本サイトカイン・インターフェロン学会
    • Related Report
      2021 Research-status Report
  • [Presentation] More sever ECRS patients produce more TSLP in the paranasal sinus2020

    • Author(s)
      Akiko Inoue, Yuriko Tanaka, Motonari Kondo, Hidehito Matsui, Takara Nakazawa, Shinya Ohira, Hirosi Osafune, Kota Wada
    • Organizer
      JSA/WAO Joint COngress 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] シェーグレンシンドローム疾患モデルマウス血清中代謝産物の解析2019

    • Author(s)
      田中ゆり子、小野里磨優、福島健、近藤元就
    • Organizer
      日本トリプトファン研究会 第39回学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 慢性副鼻腔炎患者の副鼻腔粘膜浸潤細胞の免疫学的検討2019

    • Author(s)
      井上彰子、田中ゆり子、長舩大士、近藤元就、和田弘太
    • Organizer
      第二回日本アレルギー学会関東地方会
    • Related Report
      2019 Research-status Report
  • [Presentation] シェーグレン症候群疾患モデルマウスの病態解析と発症初期新規マーカーの探索2019

    • Author(s)
      田中ゆり子、井上彰子、小野里磨優、福島健、近藤元就
    • Organizer
      第28回日本シェーグレン症候群学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] LC-MS/MSによるシェーグレン症候群疾患モデルマウス血清中L-トリプトファンおよびL-キヌレニンの定量2019

    • Author(s)
      小野里磨優、田中ゆり子、井上彰子、近藤元就、福島健
    • Organizer
      第32回バイオメディカル分析科学シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] IL-7受容体α鎖新規subdomainの同定2019

    • Author(s)
      近藤元就、葛西宏威、松井幸英、中島耕一、桑原卓
    • Organizer
      Kyoto T cell Conference 第29回学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] New findings of eosinophilic chronic rhinosinusitis tissue- significantly higher CD4 positive T cells / B cells ratio in the mucosa-.2019

    • Author(s)
      Akiko Inoue、Yuriko Tanaka、Motonari Kondo
    • Organizer
      The 48th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2019 Research-status Report
  • [Presentation] Lack of SATB1 leads to Sjogren's syndrome like autoimmune manifestations in mice.2019

    • Author(s)
      Yuriko Tanaka、Akiko Inoue、Taku Kuwabara、Taku Naito、Motonari Kondo
    • Organizer
      The 48th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2019 Research-status Report
  • [Presentation] Effect of Satb1 deficiency on differentiation of CD4+ vs CD8+ SP thymocytes.2019

    • Author(s)
      Taku Naito、Yuriko Tanaka、Taku Kuwabara、Motonari Kondo
    • Organizer
      The 48th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2019 Research-status Report
  • [Presentation] Mitochondrial respiration is critical for TCR signaling via an oxidative inactivation of phosphatase.2019

    • Author(s)
      Taku Kuwabara, Marii Ise, Taku Naito, Yuriko Tanaka, Motonari Kondo
    • Organizer
      The 42nd annual meeting of the molecular biology society of Japan
    • Related Report
      2019 Research-status Report
  • [Presentation] High CD4+ T Cell/ B Cell Ratios in the Paranasal Sinus Mucosae with Eosinophilic Chronic Rhinosinusitis.2019

    • Author(s)
      Akiko Inoue、Yuriko Tanaka、Hanae Furuya、Riko Kajiwara、Akira Fukuo、Kota Wada、Motonari Kondo
    • Organizer
      52nd Annual Meeting Of The Society For Leukocyte Biology
    • Related Report
      2019 Research-status Report
  • [Presentation] Lack of SATB1 leads to Sjogren's syndrome like autoimmune manifestations in mice2019

    • Author(s)
      Yuriko Tanaka、Akiko Inoue、Taku Naito、Taku Kuwabara、Motonari Kondo
    • Organizer
      52nd Annual Meeting Of The Society For Leukocyte Biology
    • Related Report
      2019 Research-status Report
  • [Presentation] SATB1, A Nuclear Protein Necessary for Establishment of Immune Tolerance.2019

    • Author(s)
      Motonari Kondo
    • Organizer
      52nd Annual Meeting Of The Society For Leukocyte Biology
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] T細胞に関連する疾病の治療及び診断のための薬剤を同定するための方法2019

    • Inventor(s)
      桑原卓、松井幸英、近藤元就
    • Industrial Property Rights Holder
      学校法人東邦大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Acquisition Date
      2021
    • Related Report
      2021 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi