Regulation of type-2 immune cells in chronic allergic airway inflammation.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08786
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Matsushita Kazufumi 兵庫医科大学, 医学部, 講師 (20581549)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 慢性アレルギー / 気道炎症 / Th2 / ILC2 / IgE

Outline of Final Research Achievements

Allergic airway inflammation caused by chronic exposure to allergens persists long after ceasing the allergen exposure. Here, we examined if regulating the degradation of Regnase-1, an immune-regulatory RNase, could ameliorate symptoms of chronic allergic airway inflammation. Compared with wild-type mice, Regnase-1 AA mice, a mouse strain expressing S435A/S439A mutant Regnase-1 resistant to IKK-mediated degradation, showed reduced airway eosinophilia and systemic IgE/IgG1 production in response to chronic exposure to multiple allergens. In addition, after ceasing the allergen exposure, goblet cells disappeared more quickly in the lungs in Regnase-1 AA mice compared with wild-type controls. Furthermore, although lung IL-5/IL-13-producing ILC2 and Th2 cells increased after ceasing allergen exposure, Regnase-1 AA mice showed a milder phenotype. These results suggest that regulating Regnase-1 degradation could facilitate recovery from chronic allergic airway inflammation.

Free Research Field

免疫学・アレルギー学

Academic Significance and Societal Importance of the Research Achievements

気道へのアレルゲンの長期曝露により、内因性の炎症性サイトカインの産生→2型免疫細胞の活性化による負のスパイラルが形成され、炎症の悪化、症状の持続へとつながるものと考えられる。IKK依存的なRegnase-1の分解を抑制することにより、IL-33誘導性の2型自然リンパ球（ILC2）やTh2細胞の活性化が抑制されることにより、これらの負のスパイラルを停止し、炎症の抑制、回復の促進へとつながるものと考えられる。本研究により、Regnase-1の分解を抑制することで慢性アレルギー性気道炎症の発症を抑制、または発症後の回復を促進しうる可能性が示された。