The mechanism of RSV-induced exacerbation of asthma

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K08618
• 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: Tokyo Medical University ; National Institute of Infectious Diseases (2019)
• Principal Investigator: Shibata Takehiko 東京医科大学, 医学部, 准教授 (00739196)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 喘息 / 増悪 / RSウイルス / MMP-12 / M2様マクロファージ / 好中球

Outline of Final Research Achievements

Respiratory syncytial virus (RSV) infection often exacerbates bronchial asthma. In this study we show that RSV-induced alveolar macrophages, which produce high levels of matrix metalloproteinase-12 (MMP-12), exacerbate allergic airway inflammation with increased neutrophil infiltration. When mice subjected to allergic airway inflammation via exposure to the house dust mite antigen (HDM) were infected with RSV (HDM/RSV), MMP-12 expression, neutrophil infiltration, and airway hyperresponsiveness (AHR) were increased compared to those in the HDM and RSV groups. Increased neutrophil counts and AHR in the HDM/RSV group were attenuated in MMP-12-deficient mice and mice treated with MMP408, a selective MMP-12 inhibitor, but not dexamethasone. Thus, targeting MMP-12 represents a potentially novel therapeutic strategy for the exacerbation of asthma.

Free Research Field

感染免疫学

Academic Significance and Societal Importance of the Research Achievements

RSウイルス感染に伴い喘息が増悪することはよく知られていた。この増悪のメカニズムを解明する中で、MMP-12というタンパク質が好中球 (しばしば難治性喘息において増加している) を多く気道に集積させることにより、喘息を増悪させることを明らかにした。これらの結果から、MMP-12やMMP-12産生細胞を標的とした喘息の増悪や難治性喘息に対する治療薬の開発につながることが期待される。