Functional analysis of TARC/CCL17 on a model of smoke-induced emphysema

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16134
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Yamagata University
• Principal Investigator: Sato Kento 山形大学, 医学部, 助教 (60723749)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: COPD

Outline of Final Research Achievements

It is reported that TARC/CCL17 is related to decreased respiratory function in COPD patients. We used knockout mice to examine how TARC/CCL17 and its receptor CCR4 are involved in the pathology of COPD. In TARC/CCL17 knockout mice, emphysema formation after elastase administration and macrophage accumulation after short-term cigarette smoke exposure were reduced. In CCR4 knockout mice, macrophage accumulation after short-term cigarette smoke exposure and emphysema formation after long-term smoking exposure were reduced. These results suggest that the TARC/CCL17-CCR4 pathway is involved in macrophage accumulation and is involved in the pathology of cigarette smoke-induced inflammation and emphysema formation.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

TARC/CCL17はこれまでに主にアレルギー疾患での解析が多く、COPDの病態形成に関して、どのような役割があるのかという機能解析はこれまでに報告がない。またTARC/CCL17はTh2細胞のケモカインと認識されており、マクロファージに対する作用の報告は少なく、明らかになっていない点が多い。今回、ノックアウトマウスに対して研究を行ったことで、病態の解明に近づくことが出来た。今後更に研究を続けることで、COPDの病態への理解や、治療薬の開発といった医学の進歩に大きく貢献できると考える。