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Strategy for the Development of a Novel Treatment for Severe Interstitial Pneumonia Complicated by Autoimmune Myositis

Research Project

Project/Area Number 21K08478
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 InstitutionDokkyo Medical University

Principal Investigator

Kurasawa Kazuhiro  獨協医科大学, 医学部, 特任教授 (30282479)

Co-Investigator(Kenkyū-buntansha) 有馬 雅史  獨協医科大学, 医学部, 教授 (00202763)
大和田 高義  獨協医科大学, 医学部, 講師 (30456016)
田中 彩絵  獨協医科大学, 医学部, 助教 (30743067)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsinterstitial pneumonia / 間質性肺炎 / 皮膚筋炎 / マクロファージ / 自己免疫疾患 / 筋炎 / 重症肺炎
Outline of Research at the Start

膠原病に伴う肺疾患は生命予後という点から見て最も重要な合併症であり、治療法は確立していない.その病態は十分に解明されていない.最近,我々は,2本鎖RNA編集酵素であるADAR1の遺伝子改変マウスの研究を通してマクロファージ活性化による重症間質性肺炎モデルを確立した.そこで,本研究では自己免疫疾患合併の難治性間質性の病態制御機構の解明と新規根治的治療法の開発を目指した基盤研究を行う.

Outline of Final Research Achievements

Pulmonary disease associated with collagen disease is the most important complication in terms of prognosis. In particular, interstitial pneumonia (ILD), a complication of anti-MDA5 antibody-positive dermatomyositis, is a rapidly progressive disease with a poor prognosis, and no treatment has been established. Although it has been reported that increased production of multiple inflammatory cytokines and macrophage activation may be involved in ILD, the pathogenesis is not fully understood. We established a model of rapidly progressive hyperinflammatory ILD in mice with macrophage-specific deficiency of ADAR1, a double-stranded RNA editing enzyme. This study revealed that dysfunction of ADAR1 in macrophages induces hyperfunction of MDA5, which is deeply involved in the progression of severe lung inflammation due to hyperimmune and inflammatory responses.

Academic Significance and Societal Importance of the Research Achievements

本研究は自己免疫疾患で発症する間質性肺炎の急速に難治化する過程に誘導されるサイトカインスト―ムにおいて,特に重要とされるマクロファージの活性化に注目し,ヒト臨床研究と遺伝子改変マウスを利用した動物実験を行った.その結果,過剰炎症性肺炎の難治性病態におけるマクロファージのADAR1機能の異常に病理的意義が見出された.この点において学術的意義があると思われる.また,間質性肺炎の難治化メカニズムの解明を目的とした本研究は,予後が極めて不良の抗MDA5抗体陽性間質性肺炎の病態の解明および、その根治的治療の開発に向けた基盤的研究である点において社会的意義があると思われる.

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (3 results)

All 2023 2022

All Journal Article (2 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Differences and similarities in cytokine profiles of macrophage activation syndrome in systemic lupus erythematosus and adult-onset Still’s disease2023

    • Author(s)
      Hiyama Tomoka、Kurasawa Kazuhiro、Hasegawa Anna、Miyao Tomoyuki、Tanaka Ayae、Arai Satoko、Arima Masafumi、Maezawa Reika
    • Journal Title

      Clinical and Experimental Medicine

      Volume: 23 Issue: 7 Pages: 3407-3416

    • DOI

      10.1007/s10238-023-00988-4

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Changing patterns of pulmonary abnormalities in rheumatoid arthritis2023

    • Author(s)
      Tanaka Ayae、Kurasawa Kazuhiro、Soda Sayo、Takamura Yuta、Miyao Tomoyuki、Hasegawa Anna、Hiyama Tomoka、Yamazaki Ryutaro、Arai Satoko、Owada Takayoshi、Arima Masafumi、Arakawa Hiroaki、Maezawa Reika
    • Journal Title

      Respiratory Investigation

      Volume: 61 Issue: 1 Pages: 27-39

    • DOI

      10.1016/j.resinv.2022.09.002

    • Related Report
      2023 Annual Research Report
  • [Presentation] ADAR1 in bronchial epithelial cells is involved in the airway mucosal immune system in a mouse model of asthma2022

    • Author(s)
      田中彩絵
    • Organizer
      日本免疫学会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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