摘要
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.
原文 | English |
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頁(從 - 到) | 2330-2341 |
頁數 | 12 |
期刊 | Cell Reports |
卷 | 23 |
發行號 | 8 |
DOIs | |
出版狀態 | Published - 22 5月 2018 |