Elucidation of the Pathological Functions of Bronchial Epithelial Cells and Development of Innovative Therapies for Acute Interstitial Pneumonia

2024 Fiscal Year Final Research Report

• Project/Area Number: 22K08265
• 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: Dokkyo Medical University
• Principal Investigator: Tanaka Ayae 獨協医科大学, 医学部, 助教 (30743067)
• Co-Investigator(Kenkyū-buntansha): 有馬 雅史 獨協医科大学, 医学部, 教授 (00202763) ; 倉沢 和宏 獨協医科大学, 医学部, 特任教授 (30282479) ; 大和田 高義 獨協医科大学, 医学部, 講師 (30456016)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Keywords: 間質性肺炎

Outline of Final Research Achievements

This study aimed to elucidate the pathological significance of bronchial epithelial cells and the functional role of the double-stranded RNA-editing enzyme ADAR1 in the airway epithelium immune system network, which is presumed to be a common pathological mechanism underlying rapidly progressive interstitial lung diseases (RP-ILD) of various etiologies. Using wild-type (WT) mice and airway epithelial cell-specific Adar1-deficient mice (CC10-Adar1-cKO), we analyzed a bleomycin-induced model of idiopathic pulmonary fibrosis (IPF). Our findings demonstrated that bronchial epithelial cells contribute to the pathogenesis of ILD, and that ADAR1 dysfunction exacerbates inflammation-independent progression of IPF.

Free Research Field

リウマチ学

Academic Significance and Societal Importance of the Research Achievements

本研究はIPFや感染症で発症するRP-ILDの病態に対するII型肺胞上皮細胞とClub細胞の病理的意義の解明を目的とした．我々が樹立したCC10-Adar1-cKOマウスを用いてILDモデルを解析し，気道上皮細胞を介したILDの病態とADAR1機能の関係を初めて示した．今後，本研究を発端として劇症型ILDの難治化病態に共通する新たな核心的病態概念を見出すことが十分に期待される．さらに，劇症型ILDに対する根治的治療の開発に本研究の成果が応用される可能性がある点において社会的意義があると考えられる．