Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8(+) T cell differentiation.
Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8(+) T cell differentiation.
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DOI：
10.1038/ni.3438
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发表时间：
2016-06
影响因子：
30.5
通讯作者：
Powell JD
中科院分区：
文献类型：
--
作者：
Pollizzi KN;Sun IH;Patel CH;Lo YC;Oh MH;Waickman AT;Tam AJ;Blosser RL;Wen J;Delgoffe GM;Powell JD
已显示命运决定蛋白的不对称分配有助于效应和记忆CD8+ T细胞前体的产生。在这里，我们证明了mTORC 1活性的不对称分配后，幼稚的CD8+ T细胞的激活。这导致产生一个具有增加的mTORC 1活性、增加的糖酵解活性和增加的效应分子表达的子T细胞。另一个子代T细胞继承了相对低水平的mTORC 1活性，具有增加的脂质代谢，表达增加的抗凋亡分子，随后显示出增强的长期存活。从机制上讲，我们证明了TCR诱导的氨基酸转运蛋白的不对称表达与RagC介导的mTOR向溶酶体的易位之间的联系。总的来说，我们的数据为mTORC 1介导的代谢重编程如何影响T细胞的命运决定提供了重要的见解。
The asymmetric partitioning of fate determining proteins has been shown to contribute to the generation of effector and memory CD8+ T cell precursors. Here, we demonstrate the asymmetric partitioning of mTORC1 activity upon activation of naïve CD8+ T cells. This results in the generation of one daughter T cell with increased mTORC1 activity, increased glycolytic activity and increased expression of effector molecules. The other daughter T cell inherits relatively low levels of mTORC1 activity, possesses increased lipid metabolism, expresses increased anti-apoptotic molecules and subsequently displays enhanced long-term survival. Mechanistically, we demonstrate a link between TCR-induced asymmetric expression of amino acid transporters and RagC-mediated translocation of mTOR to the lysosomes. Overall, our data provide important insight into how mTORC1-mediated metabolic reprogramming affects the fate decisions of T cells.