Inhibition of COPD development by inhibiting chemokine receptor CCR4 function.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20857
• 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: Yamagata University
• Principal Investigator: Machida Hiroyoshi 山形大学, 医学部, 客員研究員 (00910382)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 慢性閉塞性肺疾患 / CC chemokine ligand 17 / CC chemokine receptor 4

Outline of Final Research Achievements

Chemokine receptor CCR4 knockout mice were exposed to cigarette smoking for 2 days. Bronchoalveolar lavage (BAL) was performed and cell counts and fractions were assessed. Even though control mice showed an increase in total cell counts and macrophage fractions in the BAL after smoking exposure, this increase was significantly suppressed in the knockout mice.
In addition, these mice were exposed to cigarette smoking to 6 months, and a histological examination was performed. The results showed that the mean linear intercept, a quantitative measure of pulmonary emphysema, was significantly reduced in knockout mice, indicating that emphysema formation in the lung was suppressed in the absence of CCR4 in mice.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

慢性閉塞性肺疾患（COPD）は世界の死因の上位を占め、呼吸機能低下による身体活動の低下は健康寿命を損なう大きな原因となる重要な疾患である。COPDは主に喫煙を原因として発症するが、喫煙者の一部にのみ発症するため何らかの喫煙感受性の存在が指摘されている。本研究により喫煙による肺組織の炎症や肺気腫形成にCCR4が関わっていることを示し、本因子がCOPD発症の病態形成に大きな役割を持つ可能性があることを示唆した。現在COPDの発症を予防したり根治したりする方法は存在しないため、本研究は将来COPDの治療や発症予防に対し、創薬を期待することができる大変意義深いものである。