Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells
Rong En Tay, Olamide Olawoyin, Paloma Cejas, Yingtian Xie, Clifford A. Meyer, Yoshinaga Ito, Qing Yu Weng, David E. Fisher, Henry W. Long, Myles Brown, Hye‐Jung Kim, Kai W. Wucherpfennig
Abstract
Cytotoxic T cells play a key role in adaptive immunity by killing infected or cancerous cells. While the transcriptional control of CD8 T cell differentiation and effector function following T cell activation has been extensively studied, little is known about epigenetic regulation of these processes. Here we show that the histone deacetylase HDAC3 inhibits CD8 T cell cytotoxicity early during activation and is required for persistence of activated CD8 T cells following resolution of an acute infection. Mechanistically, HDAC3 inhibits gene programs associated with cytotoxicity and effector differentiation of CD8 T cells including genes encoding essential cytotoxicity proteins and key transcription factors. These data identify HDAC3 as an epigenetic regulator of the CD8 T cell cytotoxicity program.