Elucidation of the mechanism of eosinophil degranulation associated with cell death and its application to the evaluation of disease(Fostering Joint International Research)

2019 Fiscal Year Final Research Report

• Project/Area Number: 15KK0329
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Akita University
• Principal Investigator: Ueki Shigeharu 秋田大学, 医学系研究科, 准教授 (60361234)
• Project Period (FY): 2016 – 2019
• Keywords: 好酸球 / ETosis / 脱顆粒 / ヒストン / DNA / 細胞外トラップ

Outline of Final Research Achievements

In this international collaborative study, the mechanisms that determine eosinophil cell death (ETosis) in allergic diseases and the relationship between ETosis and pathogenesis in actual inflammatory tissues were elucidated. In allergic bronchopulmonary aspergillosis, eosinophil ETosis occurs at the site of inflammation and the mechanism of pathogen-induced ETosis was clarified. In addition, the presence of ETosis in eosinophilic otitis media and eosinophilic rhinosinusitis was also demonstrated. Charcot-Leiden crystals, galectin-10, chemokines, and extracellular vesicles were shown to be possible markers of allergic disease. These results have been reported in international journals and may provide the basis for future therapeutic strategies.

Free Research Field

アレルギー学

Academic Significance and Societal Importance of the Research Achievements

アレルギー疾患は頻度が高く増加傾向にある。なかでも難治性の好酸球性炎症疾患は医療費でも大きな割合を占め、世界的な問題になっている。本研究結果は、種々の難治性疾患のメカニズムを好酸球の細胞生物学的側面から明らかにしたものである。既存の概念にはなかった好酸球の細胞死という新しい視点から病態を理解することで、将来的な疾患モニタリングや治療に向けた道筋となる研究である。成果は複数の論文として当該分野のトップジャーナルを含む定評のある国際誌に掲載され、国内・国際学会の招請講演、依頼総説などを多く受けており、学術的な反響も大きかった。