Slc3a2 Mediates Branched-Chain Amino-Acid-Dependent Maintenance of Regulatory T Cells
| Autor: | Kiyoshi Takeda, Hisako Kayama, Koji Yasutomo, Makoto Kinoshita, Takashi Kurakawa, Yoshikatsu Kanai, Shimon Sakaguchi, Yasunori Shintani, Seiji Takashima, Shushi Nagamori, Mari Murakami, Ayatoshi Andou, Morihiro Ito, Norihisa Mikami, Ryu Okumura, Pornparn Kongpracha, Eiji Umemoto, Kayo Ikeda, Satoko Ueno, Keiichi Ozono, Hideki Tsumura |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Fusion Regulatory Protein 1 Heavy Chain Branched-chain amino acid Inflammation chemical and pharmacologic phenomena mTORC1 Biology Mechanistic Target of Rapamycin Complex 1 T-Lymphocytes Regulatory General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Immune system In vivo medicine Animals Amino acid transporter lcsh:QH301-705.5 chemistry.chemical_classification Mice Inbred BALB C FOXP3 hemic and immune systems Forkhead Transcription Factors Amino acid Cell biology Mice Inbred C57BL 030104 developmental biology chemistry lcsh:Biology (General) 030220 oncology & carcinogenesis Immunology medicine.symptom Amino Acids Branched-Chain |
| Zdroj: | Cell Reports, Vol 21, Iss 7, Pp 1824-1838 (2017) |
| ISSN: | 2211-1247 |
| Popis: | Summary: 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. : Treg cells regulate excess immune responses and are highly proliferative in vivo. Ikeda et al. find that branched-chain amino acids (BCAAs) are essentially required to maintain expansion and the suppressive capacity of Treg cells via Slc3a2 and mTORC1. Keywords: Treg cells, amino acids, immunometabolism, immune regulation, transporter |
| Databáze: | OpenAIRE |
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