論文 - 詳細
| RRC ID | 44648 |
|---|---|
| 著者 | Hayashi K, Jutabha P, Endou H, Sagara H, Anzai N. |
| タイトル | LAT1 is a critical transporter of essential amino acids for immune reactions in activated human T cells. |
| ジャーナル | J Immunol |
| Abstract |
Activation of T cells accompanies remarkable enhancement of metabolism. Sufficient and continuous nutrient supply is therefore important to support immune reaction in T cells. However, the mechanism of the promotion of nutrient incorporation in activated T cells has not been elucidated. In this study, we show that L-type amino acid transporter 1 (LAT1) is a major transporter for essential amino acids into activated human T cells. CD3/CD28 stimulation in primary human T cells triggered dramatic induction of LAT1 expression mediated by NF-κB and AP-1. Functional disturbance of LAT1 by a specific inhibitor and by small interfering RNA in human T cells suppressed essential amino acid uptake and induced a stress response mediated by DNA damage-inducible transcript 3 to attenuate cytokine production via inhibition of NF-κB and NFAT activities. These results uncover the previously unknown mechanism by which T cells accelerate essential amino acid uptake upon activation and adapt to essential amino acid starvation. Our results also raise the possibility for application of an LAT1 inhibitor as a new drug for therapy of disease caused by exaggerated immune response. |
| 巻・号 | 191(8) |
| ページ | 4080-5 |
| 公開日 | 2013-10-15 |
| DOI | 10.4049/jimmunol.1300923 |
| PII | jimmunol.1300923 |
| PMID | 24038088 |
| MeSH | Amino Acid Transport Systems Amino Acids, Essential / metabolism* Biological Transport CD28 Antigens / metabolism CD3 Complex / metabolism Cells, Cultured Humans Large Neutral Amino Acid-Transporter 1 / genetics Large Neutral Amino Acid-Transporter 1 / metabolism* Lymphocyte Activation* NF-kappa B / metabolism NFATC Transcription Factors / metabolism RNA Interference RNA, Small Interfering T-Lymphocytes / immunology* T-Lymphocytes / metabolism* Transcription Factor AP-1 / metabolism Transcription Factor CHOP / metabolism |
| IF | 4.886 |
| 引用数 | 61 |
| WOS 分野 | IMMUNOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | Junket |