Products Cited in Publications Worldwide Nrf2 drives activation-driven expansion of CD4+ T cells by modulating glucose and glutamine metabolism

Nrf2 drives activation-driven expansion of CD4+ T cells by modulating glucose and glutamine metabolism

Tripathi, Aprajita; Dasgupta, Debolina; Dahabieh, Michael S; Griffard-Smith, Rachel; Pant, Anil; Bugbee, Ashlyn; Yellapu, Nanda Kumar; Burt, Emily; Choi, Ben HY; Ellis, Abigail E

DOI: PMID:

Abstract

Upon antigenic stimulation, CD4+T cells undergo clonal expansion elevating their bioenergetic demands and utilization of nutrients like glucose and glutamine. The (Nrf2) is a well-known regulator of oxidative stress, but its involvement in modulating the metabolism of CD4+T cells remains unexplored. We report that protein levels are temporally regulated in activated CD4+T cells, with elevated expression during early activation followed by a decline. T cell-specific constitutive activation of , by deletion of its negative regulator Keap1, enhances early activation and interleukin-2 (IL-2) expression, upregulates T cell receptor (TCR) signaling, and increases activation-driven expansion of CD4+T cells. Mechanistically, elevated activity in activated CD4+T cells increases chromatin accessibility and proliferation-associated gene expression. Metabolically, high alters glucose metabolism and promotes glutamine metabolism via glutaminolysis to support CD4+T cell hyperproliferation. In summary, we elucidate the role of beyond traditional antioxidation in modulating the activation-driven expansion of CD4+T cells by influencing their nutrient metabolism and gene expression.

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