|Title:||Equilibrative Nucleoside Transporter 3 Regulates T Cell Homeostasis by Coordinating Lysosomal Function with Nucleoside Availability||Authors:||Wei, Chin-Wen
Dzhagalov, Ivan L
|Keywords:||ENT3; Slc29a3, lysosome; T cell; metabolism; nucleoside; nucleoside transporter||Issue Date:||22-May-2018||Publisher:||CELL PRESS||Journal Volume:||23||Journal Issue:||8||Start page/Pages:||2330||Source:||Cell reports||Abstract:||
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.
|Appears in Collections:||分子醫學研究所|
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