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ID 57486
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フルテキストURL
著者
Kunisada, Yuki Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Eikawa, Shingo Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID
Tomonobu, Nahoko Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Domae, Shohei Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Uehara, Takenori Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hori, Shohei Laboratory of Immunology and Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo
Furusawa, Yukihiro Division of Biochemistry, Keio University Graduate School of Pharmaceutical Science
Hase, Koji Division of Biochemistry, Keio University Graduate School of Pharmaceutical Science
Sasaki, Akira Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Udono, Heiichiro Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID
抄録
CD4+CD25+ regulatory T cells (Treg), an essential subset for preventing autoimmune diseases, is implicated as a negative regulator in anti-tumor immunity. We found that metformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103+KLRG1+ population, and also decreased effector molecules such as CTLA4 and IL-10. Met inhibits the differentiation of naïve CD4+ T cells into inducible Treg (iTreg) by reducing forkhead box P3 (Foxp3) protein, caused by mTORC1 activation that was determined by the elevation of phosphorylated S6 (pS6), a downstream molecule of mTORC1. Rapamycin and compound C, an inhibitor of AMP-activated protein kinase (AMPK) restored the iTreg generation, further indicating the involvement of mTORC1 and AMPK. The metabolic profile of iTreg, increased Glut1-expression, and reduced mitochondrial membrane-potential and ROS production of Ti-Treg aided in identifying enhanced glycolysis upon Met-treatment. The negative impact of Met on Ti-Treg may help generation of the sustained antitumor immunity.
キーワード
Glycolysis
Regulatory T cell (Treg)
Tumor immunity
Tumor microenvironment
mTOR
発行日
2017-10-16
出版物タイトル
EBioMedicine
25巻
出版者
Elsevier Science
開始ページ
154
終了ページ
164
ISSN
23523964
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
著作権者
© 2017 The Authors.
論文のバージョン
publisher
PubMed ID
DOI
Web of Science KeyUT
関連URL
isVersionOf https://doi.org/10.1016/j.ebiom.2017.10.009
ライセンス
https://creativecommons.org/licenses/by-nc-nd/4.0/
Citation
Yuki Kunisada, Shingo Eikawa, Nahoko Tomonobu, Shohei Domae, Takenori Uehara, Shohei Hori, Yukihiro Furusawa, Koji Hase, Akira Sasaki, Heiichiro Udono, Attenuation of CD4+CD25+ Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug, EBioMedicine, Volume 25, 2017, Pages 154-164, ISSN 2352-3964, https://doi.org/10.1016/j.ebiom.2017.10.009.
助成機関名
文部科学省
助成番号
15653356
26116709