[Report] The epigenetic landscape of T cell exhaustion
Exhausted T cells in cancer and chronic viral infection express distinctive patterns of genes, including sustained expression of programmed cell death protein 1 (PD-1). However, the regulation of gene expression in exhausted T cells is poorly understood. Here, we define the accessible chromatin landscape in exhausted CD8+ T cells and show that it is distinct from functional memory CD8+ T cells. Exhausted CD8+ T cells in humans and a mouse model of chronic viral infection acquire a state-specific epigenetic landscape organized into functional modules of enhancers. Genome editing shows that PD-1 expression is regulated in part by an exhaustion-specific enhancer that contains essential RAR, T-bet, and Sox3 motifs. Functional enhancer maps may offer targets for genome editing that alter gene expression preferentially in exhausted CD8+ T cells. Authors: Debattama R. Sen, James Kaminski, R. Anthony Barnitz, Makoto Kurachi, Ulrike Gerdemann, Kathleen B. Yates, Hsiao-Wei Tsao, Jernej Godec, Martin W. LaFleur, Flavian...