Biology Newsfeed

[Report] The epigenetic landscape of T cell exhaustion

ScienceNOW - Fetched: December 1st, 2016, 3:00pm UTC

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 D. Brown, Pierre Tonnerre, Raymond T. Chung, Damien C. Tully, Todd M. Allen, Nicole Frahm, Georg M. Lauer, E. John Wherry, Nir Yosef, W. Nicholas Haining

Read more

Return to the Newsfeed