Establishment of novel asthma treatment strategies through airway remodeling repair.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02922
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Chiba University
• Principal Investigator: Nakajima Hiroshi 千葉大学, 大学院医学研究院, 教授 (00322024)
• Co-Investigator(Kenkyū-buntansha): 田中 繁 千葉大学, 医学部附属病院, 助教 (30822051) ; 岩田 有史 千葉大学, 医学部附属病院, 講師 (90436353)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Asthma / remodeling / Treg / epithelial cells

Outline of Final Research Achievements

It is commonly believed that airway remodeling in asthma is irreversible, but the scientific evidence supporting this notion is scant. Recently, epithelial stem cells have been shown to memorize past inflammation and alter their reactivity in the skin; however, the involvement of epithelial cell inflammatory memory in airway remodeling in asthma is unknown. In the present study, we comprehensively analyzed the inflammatory memory of airway epithelial cells in murine asthma models. We found that epigenetic changes in airway epithelial cells remained for a while after the disappearance of inflammation. Furthermore, after the disappearance of inflammation, airway epithelial cells produced significantly less pro-inflammatory cytokines in response to non-specific stimuli. These findings suggest that persistent epithelial cell dysfunction in asthma might be involved in the pathogenesis of airway remodeling.

Free Research Field

Allergy

Academic Significance and Societal Importance of the Research Achievements

喘息は人口の約6%が罹患する最も有病率の高いアレルギー性呼吸器疾患である。吸入ステロイド薬に加え、IgE、IL-5、IL-4/IL-13、TSLPを標的とした抗体医薬が臨床応用され、2型炎症が優位な喘息の治療選択肢は増えたが、未だに治療困難な患者が多数存在する。特に長期罹患例においては、気道リモデリングの進行により肺機能が低下する。一般に気道リモデリングは非可逆的変化と考えられており、気道リモデリングが進行した患者の治療は困難なため、アンメットメディカルニーズが存在する。本研究の達成により気道リモデリングの修復が可能になれば、長期罹患喘息の新たな治療法の開発に至る可能性がある。