https://scholars.lib.ntu.edu.tw/handle/123456789/416774
Title: | Equilibrative Nucleoside Transporter 3 Regulates T Cell Homeostasis by Coordinating Lysosomal Function with Nucleoside Availability | Authors: | Wei, Chin-Wen Lee, Chia-Ying Lee, Ding-Jin Chu, Chang-Feng Wang, Ju-Chu Wang, Tien-Chiao Jane, Wann-Neng ZEE-FEN CHANG Leu, Chuen-Miin Dzhagalov, Ivan L CHIA-LIN HSU |
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. |
URI: | 10.1016/j.celrep.2018.04.077 https://scholars.lib.ntu.edu.tw/handle/123456789/416774 |
ISSN: | 2211-1247 | DOI: | 10.1016/j.celrep.2018.04.077 |
Appears in Collections: | 分子醫學研究所 |
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