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

Area of Science:

• Immunology
• Cell Biology
• Metabolism

Background:

• T cells are critical immune cells that undergo dynamic metabolic changes for function.
• Metabolite transporters are essential for T cell metabolic reprogramming and homeostasis.
• The role of equilibrative nucleoside transporter 3 (ENT3) in T cells is largely unknown.

Purpose of the Study:

• To investigate the role of equilibrative nucleoside transporter 3 (ENT3) in T cell homeostasis and function.
• To elucidate the mechanisms by which ENT3 influences T cell metabolism and survival.

Main Methods:

• Analysis of ENT3 expression in peripheral T cells.
• Assessment of T cell proliferation, survival, and homeostasis in ENT3-deficient models.
• Examination of lysosomal integrity, mitochondrial content, reactive oxygen species levels, and DNA damage in T cells.

Main Results:

• ENT3 is highly expressed in peripheral T cells.
• ENT3 deficiency impairs T cell proliferation and survival.
• ENT3 deficiency causes lysosomal enlargement, mitochondrial accumulation, increased reactive oxygen species, and DNA damage in T cells.
• T cell lysosomes serve as a source of salvaged metabolites.

Conclusions:

• ENT3 is vital for maintaining T cell homeostasis and activation.
• ENT3 regulates lysosomal integrity and nucleoside availability, supporting T cell function.
• Targeting ENT3 could offer therapeutic strategies for immune-related disorders.