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難治疾患病態理解のための筋免疫学創成への挑戦

Research Project

Project/Area Number 22659140
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field General internal medicine (including Psychosomatic medicine)
Research InstitutionTokyo Medical and Dental University

Principal Investigator

上阪 等  東京医科歯科大学, 大学院・医歯学総合研究科, 准教授 (00251554)

Project Period (FY) 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2010: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywords多発性筋炎 / 筋免疫 / ケモカイン
Research Abstract

申請者が開発したマウス多発性筋炎モデルを用いて、自然免疫活性化因子として再生筋線維が発現するケモカインの解析を行い、筋免疫学領域を創成するとともに、筋炎発症のメカニズムに迫り、筋炎に特異性の高い治療法の開発を目指した研究を行った。方法として、筋組織からの再生筋線維単離は難しく、一方でin vitro筋線維分化は必ずしもin vivo分化を反映しない。このため、まず、CIMの筋炎組織と筋線維芽細胞株からin vitroで分化誘導した筋線維についてケモカインのRT-PCRを行った。さらに、共通発現していたケモカインについて、マウス骨格筋由来衛星細胞からin vitro分化した筋線維、in vivoにおいてbupivacaineで再生筋線維を誘導した筋からレーザーマイクロダイセクションで回収した筋線維のRT-PCRを行った。また、衛星細胞を筋線維に分化誘導する際の培養上清のELISAで蛋白レベルの評価を行った。その結果、CIM筋組織in vitroにおける筋線維芽細胞株について、mRNAレベルで4つのケモカインが共通して発現していることがわかった。さらに、これらの中で、筋衛星細胞から分化誘導した筋線維、in vivoにおける再生筋線維について、mRNA、培養上清中の蛋白質レベルでみたところ、2つが共通発現していた。また、CIM誘導後に、bupivacaineで再生筋線維を誘導したところ、筋炎を発症した。これらの成果は、筋免疫学が成立しうることを示すとともに、PM新規治療法の開発についても多くの情報を与えるものと期待される。

Report

(1 results)
  • 2010 Annual Research Report
  • Research Products

    (16 results)

All 2010

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (13 results)

  • [Journal Article] Definitive engagement of cytotoxic CD8 T cells in C protein-induced myositis, a murine model of polymyositis.2010

    • Author(s)
      Sugihara, T., N.Okiyama, M.Suzuki, K.Kohyama, Y.Matsumoto, N.Mivasaka, H.Kohsaka
    • Journal Title

      Arthritis Rheum

      Volume: 62 Pages: 3088-3092

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of CD45 isoforms correlates with differential proliferative responses of peripheral CD4+ and CD8+ T cells2010

    • Author(s)
      Seki, I., M.Suzuki, N.Miyasaka, H.Kohsaka.
    • Journal Title

      Immunol Lett

      Volume: 129 Pages: 39-46

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Current insights in polymyositis and dermatomyositis2010

    • Author(s)
      Kohsaka H
    • Journal Title

      Clin Exp Neuroimmnol

      Volume: 1 Pages: 22-32

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 膠原病内科医から見た炎症性筋疾患の基礎と臨床2010

    • Author(s)
      上阪等
    • Organizer
      第17回熊本神経カンファレンス
    • Place of Presentation
      熊本
    • Year and Date
      2010-12-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] 多発性筋炎と皮膚筋炎-膠原病内科医の診ため-2010

    • Author(s)
      上阪等
    • Organizer
      2010北海道末梢神経・筋研究会
    • Place of Presentation
      札幌
    • Year and Date
      2010-07-31
    • Related Report
      2010 Annual Research Report
  • [Presentation] 筋炎における自己反応性T細胞と炎症性サイトカイン2010

    • Author(s)
      上阪等
    • Organizer
      第6回自己免疫疾患研究会
    • Place of Presentation
      東京
    • Year and Date
      2010-07-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] 多発性筋炎・皮膚筋炎研究-静から動へ-2010

    • Author(s)
      上阪等
    • Organizer
      順天堂大学膠原病内科講演会
    • Place of Presentation
      東京
    • Year and Date
      2010-06-30
    • Related Report
      2010 Annual Research Report
  • [Presentation] Autoagressive T cells and inflammatory cytokines in autoimmune myositis.2010

    • Author(s)
      Kohsaka H
    • Organizer
      6th Annual Symposium at Rheumatism Research Institute
    • Place of Presentation
      Seoul
    • Year and Date
      2010-06-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Identification of CD8 T cell epitopes in skeletal muscle C-protein that induces experimental myositis of mice2010

    • Author(s)
      Okiyama N, et al
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Keystone
    • Related Report
      2010 Annual Research Report
  • [Presentation] Effector T cells and Local Innate Immunity Need to Act in Concert for Development of Autoimmune Myositis2010

    • Author(s)
      Okiyama N, et al
    • Organizer
      70th Annual Meeting of Society for Investigative Dearmatology
    • Place of Presentation
      Atlamta
    • Related Report
      2010 Annual Research Report
  • [Presentation] Identification of CD8 T cell epitopes in skeletal muscle C-protein that induces experimental myositis of mice2010

    • Author(s)
      Okiyama N, et al.
    • Organizer
      International Congress of Immunology
    • Place of Presentation
      Osaka
    • Related Report
      2010 Annual Research Report
  • [Presentation] Inflammatory chemokines expressed by differentiating myofibroblasts and the muscles affected by mouse model of polymyositis2010

    • Author(s)
      Maeda A, et al.
    • Organizer
      International Congress of Immunology
    • Place of Presentation
      Osaka
    • Related Report
      2010 Annual Research Report
  • [Presentation] TNFa and IL-1 blockade for treatment of a murine model of polymyositis2010

    • Author(s)
      Sugihara T, et al.
    • Organizer
      International Congress of Immunology
    • Place of Presentation
      Osaka
    • Related Report
      2010 Annual Research Report
  • [Presentation] Blockade of TNFa or IL-1 ameliorates ongoing C-protein induced myositis of mice.2010

    • Author(s)
      Sugihara T, et al.
    • Organizer
      American College of Rheumatology 74th National Meeting
    • Place of Presentation
      Atlamta
    • Related Report
      2010 Annual Research Report
  • [Presentation] Identification of CD8 T cell epitopes in skeletal muscle C-protein that induces experimental myositis of mice.2010

    • Author(s)
      Okiyama N, et al
    • Organizer
      35th Annual Meeting of Japanese Society of Investigative Dermatology
    • Place of Presentation
      Wakayama
    • Related Report
      2010 Annual Research Report
  • [Presentation] 多発性筋炎モデルマウスを用いた新治療法の開発2010

    • Author(s)
      杉原毅彦, ほか
    • Organizer
      第54回 日本リウマチ学会総会・学術集会
    • Place of Presentation
      神戸
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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