Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation.
Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation.
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T淋巴细胞调节营养摄取以满足免疫激活的代谢需求。目前的研究表明，T细胞内大中性氨基酸（LNAAs）的供应受到病原体和T细胞抗原受体（TCR）的调节。一个单一的System L转运蛋白Slc7a5介导活化T细胞中的LNAA摄取。slc7a5缺失的T细胞不能对抗原进行代谢重编程，克隆扩增和效应分化失败。Slc7a5缺失引起的代谢突变反映了LNAA亮氨酸持续摄取对哺乳动物雷帕霉素靶蛋白复合物1 （mTORC1）激活和c-myc表达的要求。因此，病原体控制System L转运体是T细胞的关键代谢检查点。
T lymphocytes regulate nutrient uptake to meet the metabolic demands of immune activation. The present study shows that the intracellular supply of large neutral amino acids (LNAAs) in T cells is regulated by pathogen and the T cell antigen receptor (TCR). A single System L transporter, Slc7a5, mediated LNAA uptake in activated T cells. Slc7a5-null T cells could not metabolically reprogram in response to antigen and failed clonal expansion and effector differentiation. The metabolic catastrophe caused by Slc7a5 loss reflects the requirement for sustained uptake of the LNAA leucine for activation of mammalian target of rapamycin complex 1 (mTORC1) and for expression of c-myc. Pathogen control of System L transporters is thus a critical metabolic checkpoint for T cells.
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影响因子：
4.1
作者：
Beugnet, A;Tee, AR;Proud, CG
通讯作者：
Proud, CG
影响因子：
64.8
作者：
Araki, Koichi;Turner, Alexandra P.;Shaffer, Virginia Oliva;Gangappa, Shivaprakash;Keller, Susanne A.;Bachmann, Martin F.;Larsen, Christian P.;Ahmed, Rafi
通讯作者：
Ahmed, Rafi
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
5.3
作者：
LINDSTEN, T;JUNE, CH;LEIDEN, JM
通讯作者：
LEIDEN, JM
影响因子：
64.5
作者：
Bar-Peled L;Schweitzer LD;Zoncu R;Sabatini DM
通讯作者：
Sabatini DM