Challenges in the Development of Novel Inhalants Mediated by the Proton-Sensing Receptor OGR1 in Airway Inflammation

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K08404
• 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: Gunma University
• Principal Investigator: Haruka Saito 群馬大学, 医学部附属病院, 助教 (80447268)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: 気道炎症 / プロトン / 気管支喘息

Outline of Final Research Achievements

It has been reported that the proton-sensing G protein-coupled receptor OGR1, which senses extracellular pH, acts as a sensor in environments with small pH changes. We used OGR1-deficient mice to analyze how OGR1 is involved in airway inflammation including asthma. OGR1 was also expressed in airway epithelial cells, airway smooth muscle cells, and other airway constituent cells, as well as CD4+ T cells obtained from parabronchial lymph nodes and splenocytes. In the hydrochloric acid-administered ARDS model, the total cell number, macrophages, and neutrophil numbers were significantly decreased in OGR1-deficient mice. Compared to the wild type, decreased IL-6 and TNF-α production in alveolar lavage fluid was observed. It was suggested that OGR1 acts to promote airway inflammation.

Free Research Field

アレルギー

Academic Significance and Societal Importance of the Research Achievements

アトピー素因を持つ気管支喘息に対しては、現在生物学的製剤の開発により、劇的な治療の発展が認められているが、非アトピー性気管支喘息に対しての治療は未だ十分だと言えない。OGR1は気道構成細胞である気道上皮細胞、気管支平滑筋細胞に特異的に発現していることから、本研究のように気道上皮細胞に傷害を起こすHDM点鼻による気管支喘息モデルや塩酸投与によるARDSモデルの解析はOGR1の役割についてより詳細に解析できる可能性がある。さらに非アトピー性気管支喘息やARDSで産生が増加するIL-6をOGR1欠損マウスで抑制することがわかったため、OGR1は気道炎症の鍵を握っている可能性が示唆された。