Analysis of cytokines involved in induction of inflammation associated with disruption of epithelial barrier

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02847
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Hiroshima University (2020); The University of Tokyo (2018-2019)
• Principal Investigator: Nakae Susumu 広島大学, 統合生命科学研究科(生), 教授 (60450409)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: アレルギー / 喘息 / サイトカイン / マウス疾患モデル

Outline of Final Research Achievements

Barrier function of epithelial cells is important for prevention of the invasion of foreign antigens in healthy persons. When the barrier function becomes dysfunctional, antigens invade the body, following by induction of local inflammation. One of the factors is protease derived from house dust mites, pollen, and so on. When mice were inhaled with proteases, necrosis of airway epithelial cells are induced, resulting in induction of eosinophilic airway inflammation. We identified cytokines such as IL-17B, IL-31 and IL-36, which were expressed during this inflammation. Using these gene-deficient mice, we found that IL-17B, IL-31 and IL-36 were involved in development of protease-induced airway inflammation.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

プロテアーゼの吸入による気道炎症は、細胞死が誘導された上皮細胞から放出されるIL-33が起点となって炎症が起こる。過去の我々の研究成果を含む多くのマウスを用いた基礎的研究成果を踏まえて、現在、欧米の製薬会社では喘息患者などの治療薬として、IL-33中和抗体の製薬化が進められている。本研究での成果、「IL-33依存的な気道炎症に関わる遺伝子IL-17B、IL-31、IL-36の同定とその機能解析」は、喘息の発症のメカニズムの全容解明に貢献できる学術的な意義に加え、これらサイトカインの中和抗体などは、新規抗体治療薬の開発といったアレルギーの予防・治療法の開発への貢献といった社会的な意義を持つ。