Wei, Chin-WenChin-WenWeiLee, Chia-YingChia-YingLeeLee, Ding-JinDing-JinLeeChu, Chang-FengChang-FengChuWang, Ju-ChuJu-ChuWangWang, Tien-ChiaoTien-ChiaoWangJane, Wann-NengWann-NengJaneZEE-FEN CHANGLeu, Chuen-MiinChuen-MiinLeuDzhagalov, Ivan LIvan LDzhagalovCHIA-LIN HSU2019-08-292019-08-292018-05-222211-124710.1016/j.celrep.2018.04.077https://scholars.lib.ntu.edu.tw/handle/123456789/416774T 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.enENT3; Slc29a3, lysosome; T cell; metabolism; nucleoside; nucleoside transporterjournal article10.1016/j.celrep.2018.04.077297918452-s2.0-85046838357WOS:000433052200012https://api.elsevier.com/content/abstract/scopus_id/85046838357