Serine Is an Essential Metabolite for Effector T Cell Expansion
Serine Is an Essential Metabolite for Effector T Cell Expansion
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DOI：
10.1016/j.cmet.2016.12.011
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发表时间：
2017-02-07
期刊：
影响因子：
29
通讯作者：
Jones, Russell G.
中科院分区：
文献类型：
--
作者：
Ma, Eric H.;Bantug, Glenn;Jones, Russell G.
在免疫挑战过程中，T淋巴细胞参与合成代谢途径，支持克隆扩增和效应功能的发展。在这里，我们报告了非必需氨基酸丝氨酸在效应T细胞反应中的关键作用。激活后，T细胞上调丝氨酸、甘氨酸、一碳（SGOC）代谢网络中的酶，迅速加快丝氨酸转化为一碳代谢的进程。我们发现细胞外丝氨酸是最佳T细胞扩增所必需的，即使在葡萄糖浓度足以支持T细胞激活、生物能量学和效应功能的情况下。限制膳食丝氨酸会损害体内病原体驱动的T细胞扩增，但不会影响整体免疫细胞稳态。从机制上讲，丝氨酸为增殖的T细胞新生核苷酸生物合成提供甘氨酸和一碳单位，甲酸中的一碳单位可以拯救T细胞免受丝氨酸剥夺。我们的数据表明丝氨酸是一种关键的免疫代谢物，通过控制T细胞增殖能力直接调节适应性免疫。
During immune challenge, T lymphocytes engage pathways of anabolic metabolism to support clonal expansion and the development of effector functions. Here we report a critical role for the non-essential amino acid serine in effector T cell responses. Upon activation, T cells upregulate enzymes of the serine, glycine, one-carbon (SGOC) metabolic network, and rapidly increase processing of serine into one-carbon metabolism. We show that extracellular serine is required for optimal T cell expansion even in glucose concentrations sufficient to support T cell activation, bioenergetics, and effector function. Restricting dietary serine impairs pathogen-driven expansion of T cells in vivo, without affecting overall immune cell homeostasis. Mechanistically, serine supplies glycine and one-carbon units for de novo nucleotide biosynthesis in proliferating T cells, and one-carbon units from formate can rescue T cells from serine deprivation. Our data implicate serine as a key immunometabolite that directly modulates adaptive immunity by controlling T cell proliferative capacity.