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
Yasutomo, Koji
Tokushima University
Tokushima University Educator and Researcher Directory
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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
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Content Type |
Journal Article
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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.
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Journal Title |
Cell Reports
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ISSN | 22111247
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Publisher | Elsevier
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Volume | 21
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Issue | 7
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Start Page | 1824
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End Page | 1838
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Published Date | 2017-11-14
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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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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
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language |
eng
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TextVersion |
Publisher
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departments |
Medical Sciences
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