2017年11月
Slc3a2 Mediates Branched-Chain Amino-Acid-Dependent Maintenance of Regulatory T Cells
CELL REPORTS
- 巻
- 21
- 号
- 7
- 開始ページ
- 1824
- 終了ページ
- 1838
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.celrep.2017.10.082
- 出版者・発行元
- CELL PRESS
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 Foxp(3+) Treg cells with defective in vivo proliferative capacity. Mice lacking Slc3a2 specifically in Foxp(3+) 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.
- リンク情報
- ID情報
-
- DOI : 10.1016/j.celrep.2017.10.082
- ISSN : 2211-1247
- PubMed ID : 29141216
- Web of Science ID : WOS:000415073200011