Role of airway epithelial basal cells in sex-dependent asthma exacerbation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17913
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: Miyasaka Tomomitsu 東北医科薬科大学, 薬学部, 講師 (50709912)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 気管支喘息 / 性差医学 / 気道上皮基底幹細胞 / IL-33 / 気道上皮組織

Outline of Final Research Achievements

To address the pathways mediating female-predominant asthma exacerbation, in the present study we examined sex-related role of airway epithelial basal cells in the enhanced asthmatic immune responses using a Dermatophagoides farirnae-induced asthma mouse model. Increased production of IL-33 from airway epithelial cells was responsible for aggravation of asthmatic airway responses in female mice. In particular, while airway epithelial basal cells exhibited female-predominant IL-33 mRNA production, airway epithelial cells other than basal cells produced comparable level of IL-33 mRNA between male and female mice. Moreover, multiple courses of allergen challenge induced female-predominant IL-33 mRNA production in airway epithelial basal cells. These data suggest that the greater amount of IL-33 production in airway epithelial cells starting from the enhanced IL-33 mRNA expression in basal cells may play an important role in female-predominant asthma exacerbation.

Free Research Field

膠原病およびアレルギー内科学

Academic Significance and Societal Importance of the Research Achievements

気道上皮組織は、アレルゲンの体内への侵入を防ぐバリア組織としての役割だけなく、喘息免疫応答である2型免疫応答を惹起する免疫細胞としての役割を合わせもつ。本研究の結果から、気道上皮基底幹細胞におけるIL-33の産生増加を抑制することにより女性における喘息免疫応答を抑制できる可能性が示唆された。さらに、喘息病態の性差形成機序には複数回のアレルゲン曝露を契機とした気道上皮基底幹細胞によるIL-33産生量の性差が関与している可能性が明らかとなった。