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Inosine is an alternative carbon source for CD8+-T-cell function under glucose restriction.
Nature Metabolism ( IF 18.9 ) Pub Date : 2020-06-15 , DOI: 10.1038/s42255-020-0219-4
Tingting Wang 1 , J N Rashida Gnanaprakasam 1 , Xuyong Chen 1 , Siwen Kang 1 , Xuequn Xu 1 , Hua Sun 2 , Lingling Liu 1 , Hayley Rodgers 1 , Ethan Miller 1 , Teresa A Cassel 3 , Qiushi Sun 3 , Sara Vicente-Muñoz 3 , Marc O Warmoes 3 , Penghui Lin 3 , Zayda Lizbeth Piedra-Quintero 4 , Mireia Guerau-de-Arellano 4 , Kevin A Cassady 1 , Song Guo Zheng 5 , Jun Yang 6 , Andrew N Lane 3 , Xiaotong Song 2, 7 , Teresa W-M Fan 3 , Ruoning Wang 1
Affiliation  

T cells undergo metabolic rewiring to meet their bioenergetic, biosynthetic and redox demands following antigen stimulation. To fulfil these needs, effector T cells must adapt to fluctuations in environmental nutrient levels at sites of infection and inflammation. Here, we show that effector T cells can utilize inosine, as an alternative substrate, to support cell growth and function in the absence of glucose in vitro. T cells metabolize inosine into hypoxanthine and phosphorylated ribose by purine nucleoside phosphorylase. We demonstrate that the ribose subunit of inosine can enter into central metabolic pathways to provide ATP and biosynthetic precursors, and that cancer cells display diverse capacities to utilize inosine as a carbon source. Moreover, the supplementation with inosine enhances the anti-tumour efficacy of immune checkpoint blockade and adoptive T-cell transfer in solid tumours that are defective in metabolizing inosine, reflecting the capability of inosine to relieve tumour-imposed metabolic restrictions on T cells.



中文翻译:

肌苷是葡萄糖限制下CD8 + -T细胞功能的替代碳源。

T细胞经过新陈代谢重新布线,以满足抗原刺激后的生物能,生物合成和氧化还原需求。为了满足这些需求,效应T细胞必须适应感染和炎症部位环境营养水平的波动。在这里,我们显示效应T细胞可以利用肌苷作为替代底物,在体外不存在葡萄糖的情况下支持细胞生长和功能。T细胞通过嘌呤核苷磷酸化酶将肌苷代谢为次黄嘌呤和磷酸化核糖。我们证明肌苷的核糖亚基可以进入中央代谢途径以提供ATP和生物合成的前体,并且癌细胞显示出利用肌苷作为碳源的多种能力。此外,

更新日期:2020-06-15
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