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New Theory-driven Treatment Development of Polymyositis and Dermatomyositis

Research Project

Project/Area Number 15H04863
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

KOHSAKA Hitoshi  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (00251554)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords多発性筋炎 / 皮膚筋炎 / Cタンパク誘導性筋炎 / インターロイキン23 / 細胞死 / 内科 / 膠原病内科 / リウマチ性疾患 / リンパ球 / I型サイトカイン / II型サイトカイン
Outline of Final Research Achievements

Based on our Seed and Soil Theory, we conducted some research studies on polymyositis and dermatomyositis (PM / DM) and report here the results of the interleukin (IL) -23 target therapy. As was reported in the patients, serum IL-23 levels were elevated in mice with C protein induced myositis (CIM), a murine model of PM. IL-23p19 was expressed by CD68+ cells in the damaged muscles from the patients. IL-23 were expressed by CD68+ cells in the muscles and draining lymph nodes from CIM mice as well as in chemically injured muscles. Thus, IL-23 production should be associated with the muscle damage. IL-23p19-null mice were resistant to CIM. Administration of anti-IL-23 receptor antibodies ameliorated CIM. When lymph node cells from the CIM mice were transferred into recipients, the myositis was transferred not only to WT but also IL-23p19-null recipients, indicating that IL-23 should activate the autoaggressive T cells. IL-23 should be a promising therapeutic target for PM/DM.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (10 results)

All 2017 2016 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Injury and subsequent regeneration of muscles activate local innate immunity to facilitate development and relapse of autoimmune myositis2015

    • Author(s)
      Kimura N, Hirata S, Miyasaka N, Kawahata K, Kohsaka H
    • Journal Title

      Arthritis Rheumatology

      Volume: 67 Issue: 6 Pages: 1107-1116

    • DOI

      10.1002/art.39592

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Study of in vitro T cell/myotube interaction disclosed invasive and cytotoxic nature of CD8+ cells enclosed in the muscle cells.2017

    • Author(s)
      Mari Kamiya, Naoki Kimura, Akito Takamura, Fumitaka Mizoguchi, Kimito Kawahata, Hitoshi Kohsaka
    • Organizer
      19th Asia Pacific League of Associations for Rheumatology Congress (APLAR 2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多発性筋炎のin vitroモデルにおいて細胞傷害性Tリンパ球は非壊死筋細胞の内部に侵入し筋細胞死を誘導する2017

    • Author(s)
      神谷 麻理、木村 直樹、高村 聡人、溝口 史高、川畑 仁人、上阪 等
    • Organizer
      第4回JCRベーシックリサーチカンファレンス
    • Related Report
      2017 Annual Research Report
  • [Presentation] 多発性筋炎における細胞傷害性 T 細胞による筋傷害のin vitro 解析2017

    • Author(s)
      神谷 麻理、木村 直樹、高村 聡人、溝口 史高、川畑 仁人、上阪 等
    • Organizer
      第45回日本臨床免疫学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 前脛骨筋を対象としたコンコトーム筋生検の有用性を示した多発性筋炎/ 皮膚筋炎の5例2017

    • Author(s)
      梅澤 夏佳、木村 直樹、上阪 等
    • Organizer
      第45回日本臨床免疫学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 多発性筋炎における細胞傷害性T細胞による筋傷害のin vitro解析2017

    • Author(s)
      神谷 麻理、木村 直樹、高村 聡人、川畑 仁人、上阪 等
    • Organizer
      第3回日本骨免疫学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Abnormal composition of circulating T and B cells in patients with polymyositis and dermatomyositis is more biased in those with interstitial lung diseases2016

    • Author(s)
      Hirokazu Sasaki, Akito Takamura, Kimito Kawahata and Hitoshi Kohsaka
    • Organizer
      American College of Rheumatology 80th National Meeting
    • Place of Presentation
      Washington, DC
    • Year and Date
      2016-11-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Altered Peripheral lymphocyte subset repertores that reflect clinical features of dermatomyositis and polymyositis2016

    • Author(s)
      Hirokazu Sasaki, Akito Takamura, Kimito Kawahata, Hitoshi Kohsaka
    • Organizer
      13th International Workshop on Autoantibodies and Autoimmunity
    • Place of Presentation
      Westin Miyako Hotel Kyoto(Kyoto,Kyoto)
    • Year and Date
      2016-10-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Interferon-gamma but not interleukin-4 restrains experimental myositis2015

    • Author(s)
      Yoko Yoshihashi-Nakazato, Kimito Kawahata, Naoki Kimura, Hitoshi Kohsaka
    • Organizer
      1st International Conference on Myositis
    • Place of Presentation
      Stockholm (Sweden)
    • Year and Date
      2015-05-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Injury And Subsequent Regeneration Of Muscles Activate Local Innate Immunity To Facilitate Development And Relapse Of Autoimmune Myositis2015

    • Author(s)
      Naoki Kimura, Shinya Hirata, Nobuyuki Miyasaka, Kimito Kawahata, Hitoshi Kohsaka
    • Organizer
      1st International Conference on Myositis
    • Place of Presentation
      Stockholm (Sweden)
    • Year and Date
      2015-05-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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