Labile iron supply governs CD8+ T cell activation and function in metabolic health and obesity

ABSTRACT: Sufficient nutrient supply is critical for CD8+ T cell activation and functions, but the role of labile iron remains unclear. Here, we find a rapid increase in the supply of labile iron in CD8+ T cells upon T-cell receptor activation. Blocking labile iron supply blunts Fe2+ influx into mitochondria and ROS production, hindering CD8+ T cell activation, while excessive labile iron content causes hyperactivation. Disrupted labile iron supply impairs the maintenance of adipose tissue CD8+ T cells. In obesity, an increase in Fe2+ influx into mitochondria enhances adipose tissue CD8+ cell functions, but weight loss normalizes CD8+ T cell iron metabolism. CD8+ cell-specific NRF2 activation boosts ferritin and lowers mitochondrial Fe2+ and ROS content in adipose tissue CD8+ cells, attenuating obesity-related adipose tissue inflammation and metabolic disorders. These results highlight the crucial role of labile iron supply in CD8+ T cell activation.

ORGANISM(S): Mus musculus

PROVIDER: GSE300965 | GEO | 2026/09/23

REPOSITORIES: GEO