The impact of the structural and functional changes of the small airways on the pathogenesis of idiopathic pulmonary fibrosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20869
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Kyoto University
• Principal Investigator: Ikezoe Kohei 京都大学, 医学研究科, 助教 (90771733)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 特発性肺線維症 / 気道上皮細胞

Outline of Final Research Achievements

In this project, we hypothesize that the dysfunction of small airway epithelial cells contributes to the lung fibrosis and the honeycomb formation in idiopathic pulmonary fibrosis (IPF).
We performed the immunofluorescence staining for proSP-C (alveolar type II cells), KRT17 (airway epithelial basal cells), and CD68 (macrophages) in the regions including small airways and parenchyma with various extent of lung fibrosis obtained from 8 patients with IPF. As a result, we found that KRT 17 were expressed in not only the basal cells in the small airways but also the metaplastic airway epithelial cells in the parenchyma, the epithelial cells covering fibroblast foci, and the epithelial cells covering microscopic honeycomb. Our results suggest the close link between KRT17 positive airway epithelial cells and the pathogenesis in IPF.

Free Research Field

医学

Academic Significance and Societal Importance of the Research Achievements

これまでIPFでは、Ⅱ型肺胞上皮細胞の機能異常が病態の本態であり、病理学的特徴とされる蜂巣肺は、肺胞領域の線維化の末期像であると考えられてきた。本結果から、近年報告されているIPFに特徴的なKRT17陽性の基底細胞様の上皮細胞が、線維化領域やfibroblast foci, 顕微鏡的蜂巣肺の領域に認められることが病理学的に証明され、気道上皮細胞の病態への関与が示唆された。将来的にこれらの細胞の遺伝子発現変化を検討できれば、IPFにおける末梢気道上皮細胞の機能異常の詳細を検討できると考えられる。