Elucidation of the pathogenesis of exacerbation of asthma associated with rhinovirus infection and its control

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K08153
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Saitama Medical University
• Principal Investigator: Nakagome Kazuyuki 埼玉医科大学, 医学部, 准教授 (60401113)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 喘息増悪

Outline of Final Research Achievements

Polymorphism of cadherin-related family member (CDHR) 3 is associated with severe exacerbation of pediatric asthma, and CDHR3 is reported to be the receptor of rhinovirus (RV)-C which causes severe disease among RV. In addition, mutations in the CDHR3 gene lead to increased cell surface expression and increased the capacity of RV-C replication. Therefore, children with CDHR3 polymorphisms may be more susceptible to RV-C infection and severe asthma exacerbations.
This study revealed that CDHR3 directly activates eosinophils and neutrophils. Activation of eosinophils and neutrophils by CDHR3 may therefore be involved in the exacerbation of airway inflammation in asthma exacerbations.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、RVの中で重篤病態を引き起こすとされる、RV-Cの受容体であるCDHR3が、好酸球及び好中球を直接活性化することが明らかとなった。ウィルス感染では好中球が重要な役割を果たすが、ウィルス感染を伴う喘息増悪では、好中球だけでなく好酸球の気道への集積がみられる。
今回の研究でCDHR3が好酸球及び好中球を直接活性化させることを明らかにした。活性化好中球は好酸球の遊走を誘導することも以前に報告しており、CDHR3は様々な機序を介して、ウィルス感染時に気道における好酸球性炎症の誘導に関与する可能性が考えられる。これら好酸球活性化機序の解明は喘息増悪の予防および治療戦略の立脚に重要と考えられた。