The development of allergic bronchopulmonary mycosis animal model with forming eosinophilic mucoid impaction in airway

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08665
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Tokai University
• Principal Investigator: Shiraishi Yoshiki 東海大学, 医学部, 特任講師 (90383736)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: アレルギー性気管支肺真菌症 / 好酸球ETosis / 気道粘液栓

Outline of Final Research Achievements

Allergic bronchopulmonary mycosis (ABPM) is an intractable allergic disease caused by allergy to fungi in the lower respiratory tract, which leads to airway obstruction and central bronchiectasis due to recurrent eosinophilic mucus plugs in the airways. This study aims to generate a mouse model of ABPM in which eosinophil ETs form mucus plugs in the airways, and to validate an ABPM treatment targeting eosinophil ET formation using this model.
Mouse eosinophils were found to be 10,000 times more resistant to ETosis than human eosinophils, and it was difficult to form mucus plugs that obstruct airways in vitro.

Free Research Field

免疫・アレルギー

Academic Significance and Societal Importance of the Research Achievements

マウスを用いた喘息モデルにおいて、好酸球が炎症を増悪させる悪役として機能していないことは、申請者の過去の報告から明らかになっている（J Allergy Clin Immunol 135(2): 451-460, 2015）.
好酸球のETosisは、ABPMの気道粘液栓、好酸球性副鼻腔炎の粘液栓、好酸球性多発血管炎性肉芽腫症（EGPA）の原因とされているが、マウスを用いたモデルでは、好酸球のETosisの感受性の違いからモデル作成は困難であることが明らかとなった。