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Context-specific requirements of Tet enzymes in the modulation of CD8 effector and memory cell fates during acute viral infection [Cut&Tag]

ABSTRACT: In response to infections, naïve CD8 T cells give rise effector and memory T cells. However, eliciting long-lived memory CD8T cells remains a challenge for many infections. DNA demethylation of cytosines within CpG dinucleotides by Tet enzymes is a key epigenetic mechanism that regulate transcriptional programs. However, their roles in CD8 T cell memory differentiation is unclear. We report that following viral infection, Tet1/3-deficient CD8 T cells preferentially differentiate into short-lived effectors and effector memory cells. Using genome-wide DNA methylation and mice, in which Tet1/3 were ablated during T cell development and in mature CD8 T cells, respectively, we established that Tet1/3 regulate these cell fates by licensing the chromatin landscape of genes downstream of T cell receptor signaling during thymic T cell maturation. These findings unveil the context-specific roles of DNA demethylation, which is essential for defining pathways that contribute to CD8 memory T cell generation against infectious diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE252582 | GEO | 2025/02/01

REPOSITORIES: GEO

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