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

• 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
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: COPD

Outline of Research at the Start

慢性閉塞性肺疾患(COPD)は喫煙などによって生じる呼吸機能の低下を伴う呼吸器疾患である。アレルギー性疾患との関連が多く報告されているTARC/CCL17が、COPD患者の呼吸機能の経年低下と関連することを認めている。COPDの病態にTARC/CCL17がどのように関与するかを明らかにすることを目的としている。

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.

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。

Research Products

• [Journal Article] Role of CC Chemokine Ligand 17 in Mouse Models of Chronic Obstructive Pulmonary Disease (2022)
  • Author(s): Machida Hiroyoshi、Inoue Sumito、Igarashi Akira、Saitoh Shinichi、Yamauchi Keiko、Nishiwaki Michiko、Nemoto Takako、Otaki Yoichiro、Sato Masamichi、Sato Kento、Nakano Hiroshi、Yang Sujeong、Furuyama Kodai、Murano Hiroaki、Ishibashi Yu、Ota Takahito、Nakayama Takashi、Shibata Yoko、Watanabe Masafumi
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology Volume: 66 Issue: 4 Pages: 428-438
  • DOI: 10.1165/rcmb.2021-0069oc
  • Peer Reviewed / Open Access