Molecular mechanisms by which the immune response to dermatomyositis-specific self-antigens forms the pathology of dermatomyositis

• Project/Area Number: 18H02829
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Osaka University (2019-2020); University of Tsukuba (2018)
• Principal Investigator: FUJIMOTO MANABU 大阪大学, 医学系研究科, 教授 (90272591)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: 膠原病 / 自己免疫 / T細胞 / 皮膚免疫 / 皮膚 / 免疫

Outline of Final Research Achievements

Dermatomyositis is one of the connective tissue diseases and is included in the designated intractable diseases in Japan. Until now, there have been few suitable mouse models for this disease, which has been a barrier to elucidation of its pathophysiology and development of treatment methods. In recent years, disease-specific autoantibodies have been identified in dermatomyositis, and it is considered that this immune response may be the key to clarify the molecular mechanisms of the disease. In this study, we have established a mouse model that induces experimental myositis by immunizing the human TIF1γ protein, which is a major target of such autoantibodies.

Academic Significance and Societal Importance of the Research Achievements

抗TIF1γ抗体は皮膚筋炎の代表的な自己抗体であり、本抗体陽性の皮膚筋炎患者は、小児であれば顕著な筋力低下、成人であれば内臓悪性腫瘍の合併も高率であり、現在のところ、非特異的な免疫抑制療法のみである。本研究で樹立したマウスモデルは、患者の体内で起こっている自己免疫機序を忠実に模していると考えられ、より特異的な筋炎治療法の開発に貢献することが期待される。

Research Products

• [Journal Article] Immune response to dermatomyositis-specific autoantigen, transcriptional intermediary factor 1γ can result in experimental myositis. (2021)
  • Author(s): Okiyama N, Ichimura Y, Shobo M, Tanaka R, Kubota N, Saito A, Ishitsuka Y, Watanabe R, Fujisawa Y, Nakamura Y, Murakami A, Kayama H, Takeda K, Fujimoto M
  • Journal Title: Ann Rheum Dis Volume: N.A. Issue: 9 Pages: 1201-1208
  • DOI: 10.1136/annrheumdis-2020-218661
  • Peer Reviewed
• [Journal Article] Distinct Histopathologic Patterns of Finger Eruptions in Dermatomyositis Based on Myositis-Specific Autoantibody Profiles (2019)
  • Author(s): Okiyama Naoko、Yamaguchi Yukie、Kodera Masanari、Hamaguchi Yasuhito、Yokozeki Hiroo、Ishiguro Naoko、Fujimoto Manabu
  • Journal Title: JAMA Dermatology Volume: 155 Issue: 9 Pages: 1080-1080
  • DOI: 10.1001/jamadermatol.2019.1668
  • Peer Reviewed