Pathogenesis via a novel type 2 alveolar epithelial cell subgroup in COPD

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02930
• 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: Jikei University School of Medicine
• Principal Investigator: Fujita Yu 東京慈恵会医科大学, 医学部, 准教授 (10737133)
• Co-Investigator(Kenkyū-buntansha): 荒屋 潤 東京慈恵会医科大学, 医学部, 教授 (90468679)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: COPD / II型肺胞上皮

Outline of Final Research Achievements

Type II alveolar epithelial cells (AT2) are cells with heterogeneous morphology, including stemness as stem cells, and changes in AT2 morphological heterogeneity and reduced stemness may be involved in disease progression. We investigated AT2 plasmatic heterogeneity in diseased lungs by single-cell transcriptomic analysis. As a result, we identified an inflammatory AT2 (iAT2) trajectory that differentially transforms into an AT2 population that highly expresses inflammatory molecules. In this study, we will analyze the role of iAT2 in the pathogenesis of COPD and its functional analysis, which will lead to the elucidation of the pathogenesis of intractable respiratory diseases as well as the development of novel AT2-targeted therapies.

Free Research Field

呼吸器病学

Academic Significance and Societal Importance of the Research Achievements

AT2がCOPD病態で重要であることは、従来から報告されているが、AT2の形質の不均一性や新規細胞集団の有無などの詳細は検討されてこなかった。本研究の成果から、iAT2がCOPDの発症や病態に関与する詳細な分子メカニズムが明らかになる。現状、COPDの治療法に関しては、吸入ステロイドや気管支拡張剤などの対処療法しか治療選択肢がない。COPDの肺胞構造破壊につながるAT2の異常を標的とする新たな治療戦略は、難治性呼吸器疾患の新たな治療戦略開発につながる。