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

Molecular basis of Treg-specific TCR signaling regulation

Research Project

Project/Area Number 17K15723
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionOsaka University

Principal Investigator

Tanaka Atsushi  大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (00724105)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords免疫自己寛容 / 自己免疫病 / 制御性T細胞 / 免疫寛容 / 自己免疫
Outline of Final Research Achievements

The aim of the research was to elucidate the molecular mechanism specific to the regulation of T-cell receptor (TCR) signaling molecules in regulatory T cells. For this aim, we have analyzed transcriptional expression levels as well as protein expression levels and their modifications among each T-cell subset including regulatory T cells at physiological condition or upon TCR stimulations. Differentially expressed or modified TCR signaling molecules between regulatory T and conventional T cells were further compared with their immunobiological functions and kinetics of proliferation responses with or without TCR stimulation. The results indicated that regulatory T cells, compared with conventional T cells, constitutively maintain the activity of particular TCR signaling molecules at low levels and suggested their roles in maintaining the functions and proliferation kinetics specific to regulatory T cells

Academic Significance and Societal Importance of the Research Achievements

制御性T細胞は異常・過剰な免疫応答を抑制することから、自己免疫病をはじめとする多様な免疫関連疾患の予防に必須な細胞である。特に、制御性T細胞はTCR刺激に対して特異的な反応を示すことから、その分子的基盤の解明は制御性T細胞による免疫応答制御や免疫疾患予防において重要である。さらに、TCRシグナルに関わる遺伝子の多型は、自己免疫疾患に最も関連性が高いことから、制御性T細胞におけるTCRシグナル制御の理解は、疾患治療法の開発など社会的にも重要だと考えられる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (9 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Human FOXP3+ Regulatory T Cell Heterogeneity and Function in Autoimmunity and Cancer2019

    • Author(s)
      Wing James B.、Tanaka Atsushi、Sakaguchi Shimon
    • Journal Title

      Immunity

      Volume: 50 Issue: 2 Pages: 302-316

    • DOI

      10.1016/j.immuni.2019.01.020

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PD-1+ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer2019

    • Author(s)
      Takahiro Kamada, Yosuke Togashi, Danbee Ha, Akinori Sasaki, Yoshiaki Nakamura, Eiichi Sato, Shota Fukuoka, Yasuko Tada, Atsushi Tanaka, Akihito Kawazoe, Takahiro Kinoshita, Kohei Shitara, Shimon Sakaguchi, Hiroyoshi Nishikawa
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treg分化と機能におけるTCRシグナルの役割2019

    • Author(s)
      田中淳
    • Journal Title

      医学のあゆみ

      Volume: 268 Pages: 1086-1090

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Differential control of human Treg and effector T cells in tumor immunity by Fc-engineered anti-CTLA-4 antibody2018

    • Author(s)
      Ha Danbee、Tanaka Atsushi、Kibayashi Tatsuya、Tanemura Atsushi、Sugiyama Daisuke、Wing James Badger、Lim Ee Lyn、Teng Karen Wei Weng、Adeegbe Dennis、Newell Evan W.、Katayama Ichiro、Nishikawa Hiroyoshi、Sakaguchi Shimon
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 116 Issue: 2 Pages: 609-618

    • DOI

      10.1073/pnas.1812186116

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis2018

    • Author(s)
      Hirota Keiji、Hashimoto Motomu、Ito Yoshinaga、Matsuura Mayumi、Ito Hiromu、Tanaka Masao、Watanabe Hitomi、Kondoh Gen、Tanaka Atsushi、Yasuda Keiko、Kopf Manfred、Potocnik Alexandre J.、Stockinger Brigitta、Sakaguchi Noriko、Sakaguchi Shimon
    • Journal Title

      Immunity

      Volume: 48 Issue: 6 Pages: 1220-1232

    • DOI

      10.1016/j.immuni.2018.04.009

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulatory T cells in cancer immunotherapy2017

    • Author(s)
      Tanaka, A., and Sakaguchi, S.
    • Journal Title

      Cell Research

      Volume: 27 Issue: 1 Pages: 109-118

    • DOI

      10.1038/cr.2016.151

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Treg-specific control of TCR signaling molecules2019

    • Author(s)
      Atsushi Tanaka
    • Organizer
      Keystone Symposia: Uncovering Mechanisms of Immune-Based Therapy in Cancer and Autoimmunity (B3)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 制御性T細胞と腫瘍免疫2018

    • Author(s)
      田中淳
    • Organizer
      Immuno-Checkpoint Blockade Seminar in Osaka 2018
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Treg-specific control of TCR signaling molecules2017

    • Author(s)
      Atsushi Tanaka
    • Organizer
      第46回日本免疫学会総会・学術集会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi