Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan.
Institute of Plant and Microbial Biology, Academia Sinica, Taipei 115, Taiwan.
Cell Rep. 2018 May 22;23(8):2330-2341. doi: 10.1016/j.celrep.2018.04.077.
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.
T 细胞是一种多功能免疫细胞群体，通过分化和增殖，随后收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，这一过程需要代谢物转运体的积极参与。在这里，我们表明，平衡核苷转运蛋白 3（ENT3）在周围 T 细胞中高度表达，通过支持 T 细胞的增殖和存活，在维持 T 细胞稳态方面发挥关键作用。ENT3 缺陷导致溶酶体区室增大和紊乱，导致多余的线粒体积累、细胞内活性氧升高和 T 细胞中的 DNA 损伤。我们的结果确定 ENT3 是一种重要的代谢物转运体，通过调节溶酶体完整性和核苷的可用性来支持 T 细胞稳态和激活。此外，我们发现 T 细胞溶酶体是用于存活和增殖的回收代谢物的重要来源。
