Pentose phosphate pathway inhibition metabolically reprograms CD8+ T cells and disrupts CNS autoimmunity.

ABSTRACT: Multiple sclerosis is characterized by CNS infiltration of autoreactive immune cells that drive both acute inflammatory demyelination and chronic progressive axonal and neuronal injury. Expanding evidence implicates CD8+ antineural T cells in the neurodegeneration that underlies irreversible clinical progression in multiple sclerosis, yet therapies specifically targeting this cell population are limited. CD8+ T cells from patients with MS exhibit increased engagement of the pentose phosphate pathway. Pharmacologic inhibition of the pentose phosphate pathway reduced glycolysis, glucose uptake, NADPH production, ATP production, proliferation, and proinflammatory cytokine secretion in CD8+ T cells activated by ligation of CD3 and CD28. Pentose phosphate pathway inhibition also prevented CD8+

SUBMITTER: Grund EM 

PROVIDER: S-EPMC12288970 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature