Development of nucleic acid medicine for lung fibrosis using DDS directing to immune cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17425
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Osaka University
• Principal Investigator: Takeda Takashi 大阪大学, 医学系研究科, 招へい教員 (20781793)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 肺線維症 / microRNA / 樹状細胞

Outline of Final Research Achievements

Idiopathic pulmonary fibrosis is a condition in which lung becomes scarred and breathing becomes gradually difficult. Its prognosis is poor and specified as an intractable disease. One of the mechanisms is attributed to tissue fibrosis caused by sustained inflammation in which dendritic cells play a primitive role as a control tower initiating inflammatory cascade. In this study we produced the lung fibrosis model in mice by administration of bleomycin and collected tissue dendritic cells in the fibrotic lesion of lung by a flow cytometer. RNA sequencing revealed many changes in mRNA and microRNA in dendritic cells of lung fibrosis as compared to those in normal control lung. Among them, increase were mRNA levels of CD80 and CD86 which are supposed to play a role to cause inflammation and lead to lung fibrosis. Among altered microRNA, two were found to be at low level in dendritic cells of lung fibrosis and they suppressed CD80 and CD86 levels in mouse macrophage cells.

Free Research Field

3次元ゲノム構造、免疫療法

Academic Significance and Societal Importance of the Research Achievements

特発性肺線維症 は、指定難病である特発性間質性肺炎の一つで予後不良であり、樹状細胞などの免疫細胞が病態形成に重要な役割を果たすことが示されているが、画期的な治療法がないのが現状である。本研究では、マウス肺線維症モデルを用いて病巣部に存在する樹状細胞を採取して精査し、どのような遺伝子発現変化を起こしているか、あるいはそれを制御するmicroRNAについての詳細なデータが取得できた。その中の２種のmicroRNAは、今後、肺線維症の治療剤となる可能性がある。