Nrf2 drives activation-driven expansion of CD4T cells by modulating glucose and glutamine metabolism.

Upon antigenic stimulation, CD4T cells undergo clonal expansion elevating their bioenergetic demands and utilization of nutrients like glucose and glutamine. The nuclear factor erythroid-2-related factor 2 (Nrf2) is a well-known regulator of oxidative stress, but its involvement in modulating the metabolism of CD4T cells remains unexplored. We report that Nrf2 protein levels are temporally regulated in activated CD4T cells, with elevated expression during early activation followed by a decline.

Therapeutic potential of NRF2 activating drug RTA-408 in suppressing T cell effector responses and inflammatory bowel disease.

RTA-408, also known as Omaveloxolone, is an FDA-approved drug for treating Friedrich's Ataxia, a neurological disorder. It is a triterpenoid compound that activates nuclear factor erythroid 2-related factor 2 (NRF2), a key regulator of cellular redox balance. In this study, we explored the impact of RTA-408 on T cells and evaluated its therapeutic potential in inflammatory bowel disease (IBD).

Nrf2 regulates the activation-driven expansion of CD4 T-cells by differentially modulating glucose and glutamine metabolism.

Upon antigenic stimulation, CD4 T-cells undergo clonal expansion, elevating their bioenergetic demands and utilization of nutrients like glucose and glutamine. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known regulator of oxidative stress, but its involvement in modulating the metabolism of CD4 T-cells remains unexplored. Here, we elucidate the role of Nrf2 beyond the traditional antioxidation, in modulating activation-driven expansion of CD4 T-cells by influencing their nutrient metabolism.

Beyond Antioxidation: Keap1-Nrf2 in the Development and Effector Functions of Adaptive Immune Cells.

Ubiquitously expressed in mammalian cells, the Kelch-like ECH-associated protein 1 (Keap1)-NF erythroid 2-related factor 2 (Nrf2) complex forms the evolutionarily conserved antioxidation system to tackle oxidative stress caused by reactive oxygen species. Reactive oxygen species, generated as byproducts of cellular metabolism, were identified as essential second messengers for T cell signaling, activation, and effector responses. Apart from its traditional role as an antioxidant, a growing body of evidence indicates that Nrf2, tightly regulated by Keap1, modulates immune responses and regulates cellular metabolism.