T cells are a versatile immune cell population responding to challenges by differentiation and proliferation followed by contraction and memory formation. Dynamic metabolic reprogramming is essential for T cells to meet the biosynthetic needs and the reutilization of biomolecules, processes that require active participation of metabolite transporters. Here, we show that equilibrative nucleoside transporter 3 (ENT3) is highly expressed in peripheral T cells and has a key role in maintaining T cell homeostasis by supporting the proliferation and survival of T cells. ENT3 deficiency leads to an enlarged and disturbed lysosomal compartment, resulting in accumulation of surplus mitochondria, elevation of intracellular reactive oxygen species, and DNA damage in T cells. Our results identify ENT3 as a vital metabolite transporter that supports T cell homeostasis and activation by regulating lysosomal integrity and the availability of nucleosides. Moreover, we uncovered that T cell lysosomes are an important source of salvaged metabolites for survival and proliferation.

中文翻译：

---

平衡的核苷转运蛋白3通过协调溶酶体功能与核苷可用性来调节T细胞稳态。

T细胞是一种多功能的免疫细胞群体，通过分化和增殖以及紧缩和记忆形成来应对挑战。动态代谢重编程对于T细胞满足生物合成需求和生物分子的再利用至关重要，而生物分子是需要代谢物转运蛋白积极参与的过程。在这里，我们显示出平衡的核苷转运蛋白3（ENT3）在外周T细胞中高度表达，并通过支持T细胞的增殖和存活在维持T细胞稳态中起关键作用。ENT3缺乏症导致溶酶体区室扩大和紊乱，导致多余的线粒体积聚，细胞内活性氧种类升高以及T细胞中的DNA损伤。我们的结果确定ENT3是重要的代谢物转运蛋白，可通过调节溶酶体的完整性和核苷的可用性来支持T细胞的稳态和激活。此外，我们发现T细胞溶酶体是挽救代谢产物存活和增殖的重要来源。