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Anti-aging application for repairing regulatory T cell function in systemic vasculitis

Research Project

Project/Area Number 18K08385
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionShinshu University

Principal Investigator

Shimojima Yasuhiro  信州大学, 学術研究院医学系, 准教授 (50436896)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords全身性血管炎 / 制御性T細胞 / 活性酸素 / Sirt1 / アンチエイジング / 抗酸化作用 / mTOR / レスベラトロール
Outline of Final Research Achievements

We explored the etiological mechanism for impairing functional ability of regulatory T cells (Tregs), in order to improve Tregs function, in ANCA-associated vasculitis (AAV). The phosphorylation of mTOR was found to be induced ascribable to increase in reactive oxygen species (ROS) expression and decrease in the activity of Sirt1 in Tregs, leading to impairing their suppressive function in AAV. In Tregs treated with resveratrol (RVL), their functional recovery was demonstrated; and moreover, suppressed phosphorylation of mTOR, as well as reduced ROS expression and increased activation of Sirt1, was simultaneously shown in Tregs. This study suggests that antioxidative and anti-immune aging effects by RVL may contribute to improve suppressive ability of Tregs in AAV.

Academic Significance and Societal Importance of the Research Achievements

近年、AAVをはじめリウマチ膠原病領域における治療戦略は進歩を続けているが、未だ完治は難しく再発再燃が多くの患者で経験される。本研究の成果は、本来私たちに備わった免疫制御機構の中心を担う制御性T細胞(Treg)に焦点を当てた研究であり、より生理的な手法でTregの機能回復を試みた結果であることから、将来の免疫調整療法の開発に寄与する可能性が期待される。またこの手法が治療薬の開発に結びつけば、併用によって副腎皮質ステロイドを含む従来の免疫抑制薬の減量効果に寄与できる可能性も考慮される。

Report

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

    (29 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (14 results) (of which Peer Reviewed: 10 results,  Open Access: 2 results) Presentation (13 results) (of which Int'l Joint Research: 3 results) Remarks (1 results)

  • [Int'l Joint Research] Stanford大学(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Cerebrospinal fluid levels of BAFF and APRIL as direct indicators of disease activity in anti-neutrophil cytoplasmic antibody?related hypertrophic pachymeningitis2020

    • Author(s)
      Shimojima Yasuhiro、Kishida Dai、Nomura Shun、Sekijima Yoshiki
    • Journal Title

      Clinical Rheumatology

      Volume: 39 Issue: 10 Pages: 3145-3148

    • DOI

      10.1007/s10067-020-05270-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical characteristics of patients with myalgia as the initial manifestation of small and medium-sized vasculitis: a retrospective study2020

    • Author(s)
      Ushiyama Satoru、Shimojima Yasuhiro、Ueno Ken-ichi、Kishida Dai、Miyazaki Daigo、Sekijima Yoshiki
    • Journal Title

      Rheumatology International

      Volume: 40 Issue: 10 Pages: 1667-1674

    • DOI

      10.1007/s00296-020-04652-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cerebrospinal fluid biomarkers implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody-related hypertrophic pachymeningitis2020

    • Author(s)
      Ikeda Junji、Shimojima Yasuhiro、Usami Yoko、Ueno Ken-ichi、Kishida Dai、Sekijima Yoshiki
    • Journal Title

      Clinical Rheumatology

      Volume: 39 Issue: 6 Pages: 1803-1811

    • DOI

      10.1007/s10067-020-04971-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alteration of BAFF and APRIL in the cerebrospinal fluid based on the therapeutic response in primary central nervous system B-cell lymphoma2020

    • Author(s)
      Ikeda Junji、Shimojima Yasuhiro、Yoshinaga Tsuneaki、Kodaira Minori、Nishina Sayaka、Ito Kiyoshi、Sekijima Yoshiki
    • Journal Title

      Journal of Clinical Neuroscience

      Volume: 81 Pages: 72-75

    • DOI

      10.1016/j.jocn.2020.09.005

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acquired Amegakaryocytic Thrombocytopenia in Adult-onset Still's Disease: Successful Combination Therapy with Tocilizumab and Cyclosporine2019

    • Author(s)
      Ichikawa Takanori、Shimojima Yasuhiro、Otuki Toshiaki、Ueno Ken-ichi、Kishida Dai、Sekijima Yoshiki
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 23 Pages: 3473-3478

    • DOI

      10.2169/internalmedicine.2929-19

    • NAID

      130007754647

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-12-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characteristics of circulating natural killer cells and their interferon-γ production in active adult-onset Still's disease2019

    • Author(s)
      Shimojima Yasuhiro、Kishida Dai、Ueno Ken-ichi、Ushiyama Satoru、Ichikawa Takanori、Sekijima Yoshiki
    • Journal Title

      The Journal of Rheumatology

      Volume: online first Issue: 10 Pages: 1268-1276

    • DOI

      10.3899/jrheum.181192

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Normal Pressure Hydrocephalus in Systemic Lupus Erythematosus2019

    • Author(s)
      Sakaguchi Noriko、Shimojima Yasuhiro、Ushiyama Satoru、Ichikawa Takanori、Ikeda Junji、Ueno Ken-ichi、Kishida Dai、Sekijima Yoshiki
    • Journal Title

      JCR: Journal of Clinical Rheumatology

      Volume: online first Issue: 7 Pages: 1-1

    • DOI

      10.1097/rhu.0000000000001101

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Late-onset familial Mediterranean fever in Japan2019

    • Author(s)
      Kishida Dai、Yazaki Masahide、Nakamura Akinori、Tsuchiya-Suzuki Ayako、Shimojima Yasuhiro、Sekijima Yoshiki
    • Journal Title

      Modern Rheumatology

      Volume: online first Issue: 3 Pages: 1-4

    • DOI

      10.1080/14397595.2019.1621440

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 全身性血管炎と末梢神経障害2019

    • Author(s)
      下島恭弘
    • Journal Title

      脳神経内科

      Volume: 91 Pages: 287-294

    • Related Report
      2019 Research-status Report
  • [Journal Article] ANCA関連疾患と肥厚性硬膜炎2019

    • Author(s)
      下島恭弘
    • Journal Title

      脳神経内科

      Volume: 91 Pages: 352-360

    • Related Report
      2019 Research-status Report
  • [Journal Article] 肥厚性硬膜炎2019

    • Author(s)
      下島恭弘, 関島良樹
    • Journal Title

      精神科治療学

      Volume: 34 Pages: 286-288

    • Related Report
      2019 Research-status Report
  • [Journal Article] Propylthiouracil-induced Otitis Media with Antineutrophil Cytoplasmic Antibody-associated Vasculitis2018

    • Author(s)
      Tanaka Rika、Shimojima Yasuhiro、Moteki Hideaki、Kishida Dai、Ueno Ken-ichi、Sekijima Yoshiki
    • Journal Title

      Internal Medicine

      Volume: 57 Issue: 20 Pages: 3029-3033

    • DOI

      10.2169/internalmedicine.0944-18

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2018-10-15
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 各種難病の最新治療情報・膠原病の背景と現状~治療の進歩を含めて~2018

    • Author(s)
      下島恭弘
    • Journal Title

      難病と在宅ケア

      Volume: 24 Pages: 34-39

    • NAID

      40021667849

    • Related Report
      2018 Research-status Report
  • [Journal Article] One novel and two uncommon MEFV mutations in Japanese patients with familial Mediterranean fever: a clinicogenetic study2017

    • Author(s)
      Kishida D、Yazaki M、Nakamura A、Nomura F、Kondo T、他8名
    • Journal Title

      Rheumatol Int

      Volume: 38 Issue: 1 Pages: 105-110

    • DOI

      10.1007/s00296-017-3886-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 成人スチル病における制御性T細胞の可塑性と制御機能2021

    • Author(s)
      下島 恭弘、市川貴規、岸田大、関島良樹
    • Organizer
      第65回日本リウマチ学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Relationship between interferon-γ-producing immunocompetent cells and disease activity in adult-onset Still’s disease2020

    • Author(s)
      Yasuhiro Shimojima, Dai Kishida, Takanori Ichikawa, Yoshiki Sekijima
    • Organizer
      EULAR2020 Annual European e-Congress of Rheumatology
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 成人スチル病における制御性T細胞の可塑性と疾患活動性の解析2020

    • Author(s)
      下島 恭弘、市川貴規、岸田大、関島良樹
    • Organizer
      第48回臨床免疫学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ANCA関連肥厚性硬膜炎の髄液バイオマーカー解析2020

    • Author(s)
      下島 恭弘、池田淳司、岸田大、上野賢一、関島良樹
    • Organizer
      第64回日本リウマチ学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 成人スチル病における末梢血NK細胞のインターフェロンγ産生機能2019

    • Author(s)
      下島恭弘
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] The pathogenic CSF biomarker in ANCA-related hypertrophic pachymeningitis2019

    • Author(s)
      下島恭弘
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 成人スチル病における疾患活動性とインターフェロンγ産生能の解析2019

    • Author(s)
      下島恭弘
    • Organizer
      第47回日本臨床免疫学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Cerebrospinal fluid biomarker of disease activity: significance in ANCA-related hypertrophic pachymeningitis2018

    • Author(s)
      Shimojima Y, Kishida D, Sekijima Y
    • Organizer
      2018ACR/ARHP Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ANCA関連肥厚性硬膜炎におけるBAFFおよびAPRILの病態関連研究2018

    • Author(s)
      下島恭弘
    • Organizer
      第62回日本リウマチ学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Clinical and genetic analysis of patients with symptoms mimicking familial Mediterranean fever2018

    • Author(s)
      Kishida D, Nakamura A, Yazaki M, Tsuchiya-Suzuki A, Shimojima Y, Sekijima Y
    • Organizer
      2018ACR/ARHP Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ANCA関連血管炎に合併する肥厚性硬膜炎の臨床的特徴2018

    • Author(s)
      下島恭弘、岸田大、日根野晃代、関島良樹
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 皮膚筋炎・多発性筋炎における末梢血T細胞の細胞内シグナルと動態解析2018

    • Author(s)
      下島恭弘
    • Organizer
      Rheumatology Conference 2018
    • Related Report
      2018 Research-status Report
  • [Presentation] ANCA関連肥厚性硬膜炎の髄液バイオマーカー解析2018

    • Author(s)
      下島恭弘、岸田大、関島良樹
    • Organizer
      第46回日本臨床免疫学会総会
    • Related Report
      2018 Research-status Report
  • [Remarks] 信州大学医学部内科学第三教室ホームページ

    • URL

      http://www.shinshu-u.ac.jp/faculty/medicine/chair/i-3nai/theme04.html

    • Related Report
      2019 Research-status Report

URL: 

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

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