Equilibrative Nucleoside Transporter 3 Regulates T Cell Homeostasis by Coordinating Lysosomal Function with Nucleoside Availability

Chin Wen Wei, Chia Ying Lee, Ding Jin Lee, Chang Feng Chu, Ju Chu Wang, Tien Chiao Wang, Wann Neng Jane, Zee Fen Chang, Chuen Miin Leu, Ivan L. Dzhagalov, Chia Lin Hsu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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. A sufficient supply of biomaterials is essential during T cell differentiation and proliferation. Wei et al. reveal that the nucleoside transporter ENT3 is necessary for maintaining T cell homeostasis and survival by regulating lysosome function and nucleoside availability.

Original languageEnglish
Pages (from-to)2330-2341
Number of pages12
JournalCell Reports
Volume23
Issue number8
DOIs
StatePublished - 22 May 2018

Keywords

  • ENT3
  • metabolism
  • nucleoside
  • nucleoside transporter
  • Slc29a3, lysosome
  • T cell

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