Novel pathogenesis of allergic disorders based on relative hypoxic stress

• Project/Area Number: 17H06669
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Veterinary medical science
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: Kenshiro Matsuda 東京農工大学, (連合)農学研究科(研究院), 産学官連携研究員 (70642619)
• Research Collaborator: MATSUDA hiroshi
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アレルギー / 相対的低酸素 / TRPチャネル / アナフィラキシー / TRPA1 / アトピー性皮膚炎 / マスト細胞 / 酸素センシング / 酸素応答

Outline of Final Research Achievements

Transient Receptor Potentially (TRP) Ankyrin 1, Melastatin 3 and 7 were expressed in the mast cells including bone marrow cultured mast cells (BMCMC), and skin mast cells. Especially, TRPA1 response in the mast cells clearly induced the release of β-hexosaminidase, mMCP-6, and histamine. Systemic anaphylactic phenotypes such as reduced rectal temperature, and increased vascular permiability were then indicated after relative hypoxia stress in adult C57BL/6J mice. However, each phenotypes was significantly inhibited in mast cell dificient mice and TRPA1 knockout mice.
These findings introduce a potential role of oxygen in inducing mast cell-dependent systemic anaphylaxis.

Academic Significance and Societal Importance of the Research Achievements

相対的低酸素環境下におけるマスト細胞などの各種免疫細胞の酸素センシングを担うと考えられるTRPチャネルの機能を分子解析することで、酸素起因性アレルギーの新たな病態を明らかにし、医療及び獣医療において社会的問題化しているアレルギー疾患の新規視点に基づく治療法開発の基礎的知見の獲得を目指した。すなわち、生体が曝露される大気中酸素濃度の変化、即ち相対的低酸素環境が末梢組織に存在する様々な細胞群を活性化させ、それによって生じるあるいは修飾されるアレルギー病態の解明に繋がり、酸素起因性疾患を新たに定義することが可能となる。

Research Products

• [Journal Article] Mast cell-mediated oxygen-induced retinopathy (2018)
  • Author(s): 松田研史郎、田中あかね、松田浩珍
  • Journal Title: Functional Food Research Volume: 14 Issue: 0 Pages: 4-9
  • DOI: 10.32153/ffr.14.0_4
  • NAID: 130007612139
  • ISSN: 2432-3357, 2434-3048
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Mast cells are critical for aberrant vascular remodeling of oxygen-induced retinopathy. (2018)
  • Author(s): Matsuda K, Karasawa K, Amagai Y, Arkwright PD, Kondo M, Tanaka A, Matsuda H
  • Organizer: European Academy of Allergy and Clinical Immunology Congress
  • Int'l Joint Research
• [Presentation] 肥満細胞の活性化に起因する未熟児網膜症の発病メカニズム (2018)
  • Author(s): 松田研史郎、田中あかね、松田浩珍
  • Organizer: Tokyo Biomarker Innovation Research Association Forum
• [Presentation] 未熟児網膜症病態発現機構の分子解析：マスト細胞の必要性 (2018)
  • Author(s): 松田研史郎、田中あかね、松田浩珍
  • Organizer: 日本獣医学会学術大会