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

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 processe...

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Autores principales: Tay, Rong En, Olawoyin, Olamide, Cejas, Paloma, Xie, Yingtian, Meyer, Clifford A., Ito, Yoshinaga, Weng, Qing Yu, Fisher, David E., Long, Henry W., Brown, Myles, Kim, Hye-Jung, Wucherpfennig, Kai W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336313/
https://www.ncbi.nlm.nih.gov/pubmed/32374402
http://dx.doi.org/10.1084/jem.20191453
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author Tay, Rong En
Olawoyin, Olamide
Cejas, Paloma
Xie, Yingtian
Meyer, Clifford A.
Ito, Yoshinaga
Weng, Qing Yu
Fisher, David E.
Long, Henry W.
Brown, Myles
Kim, Hye-Jung
Wucherpfennig, Kai W.
author_facet Tay, Rong En
Olawoyin, Olamide
Cejas, Paloma
Xie, Yingtian
Meyer, Clifford A.
Ito, Yoshinaga
Weng, Qing Yu
Fisher, David E.
Long, Henry W.
Brown, Myles
Kim, Hye-Jung
Wucherpfennig, Kai W.
author_sort Tay, Rong En
collection PubMed
description 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.
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spelling pubmed-73363132021-01-06 Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells Tay, Rong En Olawoyin, Olamide Cejas, Paloma Xie, Yingtian Meyer, Clifford A. Ito, Yoshinaga Weng, Qing Yu Fisher, David E. Long, Henry W. Brown, Myles Kim, Hye-Jung Wucherpfennig, Kai W. J Exp Med Article 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. Rockefeller University Press 2020-05-06 /pmc/articles/PMC7336313/ /pubmed/32374402 http://dx.doi.org/10.1084/jem.20191453 Text en © 2020 Tay et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Tay, Rong En
Olawoyin, Olamide
Cejas, Paloma
Xie, Yingtian
Meyer, Clifford A.
Ito, Yoshinaga
Weng, Qing Yu
Fisher, David E.
Long, Henry W.
Brown, Myles
Kim, Hye-Jung
Wucherpfennig, Kai W.
Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells
title Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells
title_full Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells
title_fullStr Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells
title_full_unstemmed Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells
title_short Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells
title_sort hdac3 is an epigenetic inhibitor of the cytotoxicity program in cd8 t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336313/
https://www.ncbi.nlm.nih.gov/pubmed/32374402
http://dx.doi.org/10.1084/jem.20191453
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