Elucidation of the Role of Active Sulfur Molecular Species in Innate Immune System Airway Allergy and Inflammation

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16131
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Tohoku University
• Principal Investigator: Mitsune Ayumi 東北大学, 医学系研究科, 非常勤講師 (80895904)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 気管支喘息

Outline of Final Research Achievements

The aim of this study was to clarify the effect of active sulfur species (RSS) produced by active sulfur species producing enzyme (CPERS) on type 2 airway inflammation mediated by type 2 innate immune lymphocytes (ILC2). We found that type 2 airway inflammation induced by fungal allergens and IL-33 is enhanced in CPERS heterozygous mice, and that type 2 cytokine production by IL-33-activated ILC2 is enhanced by reduced expression of CPERS. The results suggest that RSS generated by CPERS may regulate type 2 airway inflammation through an innate immune mechanism by suppressively regulating ILC2 proliferation and type 2 cytokine production.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

現在、喘息やアトピー性皮膚炎などのアレルギー疾患の難治化病態に対しては、副腎皮質ステロイドや免疫抑制剤、生物学的製剤が治療の中心となっている。現行治療は長期使用による有害事象や経済性の問題を抱えている。本研究によりRSSがILC2を介した自然免疫機序を負に制御することが示唆されたこのことは、RSSが新規アレルギー戦略として極めて適応範囲が広い創薬につながる可能性を示し、社会的に学術的だけではなく、社会的にも意義のある成果と考える。