RNA-seq Unveils that Exogenous Hemin Treatment Accelerates CD8+ T Cell Exhaustion

Regulatory heme is known to control cellular behavior by regulating the activities of hemoproteins. We hypothesized that increased levels of regulatory heme may drive T cell exhaustion. To test this, we first confirmed that treatment with hemin, a heme analog, effectively increased intracellular regulatory heme levels in T cells. To evaluate the transcriptional changes in CD8+ T cells treated with hemin, we conducted RNA sequencing on CD8+ T cells with and without exogenous hemin treatment. The RNA-seq data revealed that hemin treatment strongly modulated gene expression patterns associated with terminally exhausted T cells. Pathway enrichment analysis further revealed that hemin suppressed pathways involved in proliferation and cytokine production while altering metabolic processes, such as cholesterol efflux and fatty acid biosynthesis, which are known to regulate T cell function. These results suggest that increased levels of regulatory heme drive T cell exhaustion differentiation.