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Equilibrative Nucleoside Transporter 3 Regulates T Cell Homeostasis by Coordinating Lysosomal Function with Nucleoside Availability.
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.
Authors : Wei Chin-Wen , Lee Chia-Ying , Lee Ding-Jin , Chu Chang-Feng , Wang Ju-Chu , Wang Tien-Chiao , Jane Wann-Neng , Chang Zee-Fen , Leu Chuen-Miin , Dzhagalov Ivan L , Hsu Chia-Lin ,
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Pathways :
WP1694: Pyrimidine metabolism
WP1011: T Cell Receptor Signaling Pathway
WP1025: B Cell Receptor Signaling Pathway
WP1043: Calcium Regulation in the Cardiac Cell
WP1069: Integrin-mediated cell adhesion
WP1078: G1 to S cell cycle control
WP1083: Cell cycle
WP1130: T Cell Receptor Signaling Pathway
WP1144: B Cell Receptor Signaling Pathway
WP1159: Calcium Regulation in the Cardiac Cell
WP1185: Integrin-mediated cell adhesion
WP1195: G1 to S cell cycle control
WP1200: Cell cycle
WP1345: T Cell Receptor Signaling Pathway
WP1354: B Cell Receptor Signaling Pathway
WP1365: Calcium Regulation in the Cardiac Cell
WP1386: Integrin-mediated cell adhesion
WP1393: Cell cycle
WP1411: Cell Division: First embryonic mitosis
WP1455: Serotonin Transporter Activity
WP1493: Carbon assimilation C4 pathway
WP1596: Iron Homeostasis
WP1616: ABC transporters
WP1680: Oxidative phosphorylation
WP1689: Porphyrin and chlorophyll metabolism
Related Genes :
Bibliography :
[29791845] Equilibrative Nucleoside Transporter 3 Regulates T Cell Homeostasis by Coordinating Lysosomal Function with Nucleoside Availability.
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