| First Author | Ikeda K | Year | 2017 |
| Journal | Cell Rep | Volume | 21 |
| Issue | 7 | Pages | 1824-1838 |
| PubMed ID | 29141216 | Mgi Jnum | J:254863 |
| Mgi Id | MGI:6104045 | Doi | 10.1016/j.celrep.2017.10.082 |
| Citation | Ikeda K, et al. (2017) Slc3a2 Mediates Branched-Chain Amino-Acid-Dependent Maintenance of Regulatory T Cells. Cell Rep 21(7):1824-1838 |
| abstractText | 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. |
