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Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells.

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.

SUBMITTER: Tay RE

PROVIDER: S-EPMC7336313 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells.

Tay Rong En RE Olawoyin Olamide O Cejas Paloma P Xie Yingtian Y Meyer Clifford A CA Ito Yoshinaga Y Weng Qing Yu QY Fisher David E DE Long Henry W HW Brown Myles M Kim Hye-Jung HJ Wucherpfennig Kai W KW

The Journal of experimental medicine 20200701 7

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 in ...[more]

PMID: 32374402

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