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ID 115052
Author
Ikeda, Kayo Osaka University|Japan Agency for Medical Research and Development
Kinoshita, Makoto Osaka University|Japan Agency for Medical Research and Development
Kayama, Hisako Osaka University|Japan Agency for Medical Research and Development
Nagamori, Shushi Osaka University|Nara Medical University
Kongpracha, Pornparn Osaka University|Nara Medical University
Umemoto, Eiji Osaka University|Japan Agency for Medical Research and Development
Okumura, Ryu Osaka University|Japan Agency for Medical Research and Development
Kurakawa, Takashi Osaka University|Japan Agency for Medical Research and Development
Murakami, Mari Osaka University|Japan Agency for Medical Research and Development
Mikami, Norihisa Osaka University
Shintani, Yasunori Osaka University
Ueno, Satoko Ajinomoto
Andou, Ayatoshi EA Pharma
Ito, Morihiro Chubu University
Tsumura, Hideki National Research Institute for Child Health and Development
Ozono, Keiichi Osaka University
Takashima, Seiji Osaka University
Sakaguchi, Shimon Osaka University
Kanai, Yoshikatsu Osaka University
Takeda, Kiyoshi Osaka University|Japan Agency for Medical Research and Development
Content Type
Journal Article
Description
Foxp3+ regulatory T (Treg) cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained in vivo. Here, we show that branched-chain amino acids (BCAAs), including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers of Foxp3+ Treg cells with defective in vivo proliferative capacity. Mice lacking Slc3a2 specifically in Foxp3+ Treg cells showed impaired in vivo replication and decreased numbers of Treg cells. Slc3a2-deficient Treg cells showed impaired isoleucine-induced activation of the mTORC1 pathway and an altered metabolic state. Slc3a2 mutant mice did not show an isoleucine-induced increase of Treg cells in vivo and exhibited multi-organ inflammation. Taken together, these findings demonstrate that BCAA controls Treg cell maintenance via Slc3a2-dependent metabolic regulation.
Journal Title
Cell Reports
ISSN
22111247
Publisher
Elsevier
Volume
21
Issue
7
Start Page
1824
End Page
1838
Published Date
2017-11-14
Rights
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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DOI (Published Version)
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language
eng
TextVersion
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departments
Medical Sciences