Understanding Intractable Fungal Airway Allergy: Pathogenesis and Therapeutic Development

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08577
• 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: Oguma Tsuyoshi 東海大学, 医学部, 教授 (20255441)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: アレルギー性気管支肺真菌症 / アレルギー性気管支肺アレルギー症 / アスペルギルス / 真菌 / IL-1α / 光触媒 / 酸化チタン

Outline of Final Research Achievements

This study focused on molecules produced by airway epithelial cells directly exposed to fungi, contributing to the pathogenesis of allergic bronchopulmonary aspergillosis (ABPA). IL-1α, identified as relevant in both in vitro and in vivo models, was expressed in airway epithelial cells via a fungal antigen protease-dependent pathway involving the EGF receptor, partially mediated by TNF-α converting enzyme (TACE). Inhibiting fungal antigen protease activity through titanium dioxide photocatalytic reaction was found to be beneficial for suppressing airway allergy-related molecules of epithelial origin, such as IL-1α, similar to EGF receptor and TACE inhibitors.

Free Research Field

アレルギー学

Academic Significance and Societal Importance of the Research Achievements

本研究では、アレルギー性気管支真菌症(ABPM)の病態に関与する分子として、IL-1αを同定し、EGF受容体・TACE阻害薬と同様に、酸化チタンの光触媒反応による真菌アレルゲンの無害化がIL-1α等の気道上皮由来の気道アレルギー疾患関連分子の抑制に有用と考えられた。真菌アレルゲンの無毒化は今後、真菌アレルギーの症状の軽減・重症化予防の他、発症予防にもつながることが推測され、本研究の成果はその基礎的研究として有用と考えられた。