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Store-Operated Ca2+ Entry Controls Clonal Expansion of T Cells through Metabolic Reprogramming
Immunity ( IF 25.5 ) Pub Date : 2017-10-11 , DOI: 10.1016/j.immuni.2017.09.003
Martin Vaeth 1 , Mate Maus 1 , Stefan Klein-Hessling 2 , Elizaveta Freinkman 3 , Jun Yang 1 , Miriam Eckstein 4 , Scott Cameron 5 , Stuart E Turvey 5 , Edgar Serfling 2 , Friederike Berberich-Siebelt 2 , Richard Possemato 1 , Stefan Feske 1
Affiliation  

Store-operated Ca2+ entry (SOCE) is the main Ca2+ influx pathway in lymphocytes and is essential for T cell function and adaptive immunity. SOCE is mediated by Ca2+ release-activated Ca2+ (CRAC) channels that are activated by stromal interaction molecule (STIM) 1 and STIM2. SOCE regulates many Ca2+-dependent signaling molecules, including calcineurin, and inhibition of SOCE or calcineurin impairs antigen-dependent T cell proliferation. We here report that SOCE and calcineurin regulate cell cycle entry of quiescent T cells by controlling glycolysis and oxidative phosphorylation. SOCE directs the metabolic reprogramming of naive T cells by regulating the expression of glucose transporters, glycolytic enzymes, and metabolic regulators through the activation of nuclear factor of activated T cells (NFAT) and the PI3K-AKT kinase-mTOR nutrient-sensing pathway. We propose that SOCE controls a critical “metabolic checkpoint” at which T cells assess adequate nutrient supply to support clonal expansion and adaptive immune responses.



中文翻译:

存储操纵的 Ca2+ 进入通过代谢重编程控制 T 细胞的克隆扩增

钙库操纵的 Ca 2+进入 (SOCE) 是淋巴细胞中主要的 Ca 2+流入途径,对于 T 细胞功能和适应性免疫至关重要。SOCE 由 Ca 2+释放激活的 Ca 2+ (CRAC) 通道介导,该通道由基质相互作用分子 (STIM) 1 和 STIM2 激活。SOCE 调节许多 Ca 2+依赖性信号分子,包括钙调磷酸酶,并且 SOCE 或钙调磷酸酶的抑制会损害抗原依赖性 T 细胞增殖。我们在这里报道 SOCE 和钙调磷酸酶通过控制糖酵解和氧化磷酸化来调节静止 T 细胞的细胞周期进入。SOCE 通过激活活化 T 细胞核因子 (NFAT) 和 PI3K-AKT 激酶-mTOR 营养感应途径来调节葡萄糖转运蛋白、糖酵解酶和代谢调节剂的表达,从而指导初始 T 细胞的代谢重编程。我们认为 SOCE 控制着一个关键的“代谢检查点”,T 细胞在该检查点评估充足的营养供应以支持克隆扩张和适应性免疫反应。

更新日期:2017-10-11
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