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LAT1 Is a Critical Transporter of Essential Amino Acids for Immune Reactions in Activated Human T Cells

2013; American Association of Immunologists; Volume: 191; Issue: 8 Linguagem: Inglês

10.4049/jimmunol.1300923

1550-6606

Keitaro Hayashi, Promsuk Jutabha, Hitoshi Endou, Hironori Sagara, Naohiko Anzai,

Immune Cell Function and Interaction

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.