Histone deacetylase 3 represses cholesterol efflux during CD4+ T-cell activation

After antigenic activation, quiescent naive CD4+ T cells alter their metabolism to proliferate. This metabolic shift increases production of nucleotides, amino acids, fatty acids, and sterols. Here, we show that histone deacetylase 3 (HDAC3) is critical for activation of murine peripheral CD4+ T cel...

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Autores principales:	Drew Wilfahrt, Rachael L Philips, Jyoti Lama, Monika Kizerwetter, Michael Jeremy Shapiro, Shaylene A McCue, Madeleine M Kennedy, Matthew J Rajcula, Hu Zeng, Virginia Smith Shapiro
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	HDAC3 T cell activation cholesterol regulation Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4663fbf5394c4aa88ceec8a8cec5a37d
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spelling	oai:doaj.org-article:4663fbf5394c4aa88ceec8a8cec5a37d2021-12-02T10:27:00ZHistone deacetylase 3 represses cholesterol efflux during CD4+ T-cell activation10.7554/eLife.709782050-084Xe70978https://doaj.org/article/4663fbf5394c4aa88ceec8a8cec5a37d2021-12-01T00:00:00Zhttps://elifesciences.org/articles/70978https://doaj.org/toc/2050-084XAfter antigenic activation, quiescent naive CD4+ T cells alter their metabolism to proliferate. This metabolic shift increases production of nucleotides, amino acids, fatty acids, and sterols. Here, we show that histone deacetylase 3 (HDAC3) is critical for activation of murine peripheral CD4+ T cells. HDAC3-deficient CD4+ T cells failed to proliferate and blast after in vitro TCR/CD28 stimulation. Upon T-cell activation, genes involved in cholesterol biosynthesis are upregulated while genes that promote cholesterol efflux are repressed. HDAC3-deficient CD4+ T cells had reduced levels of cellular cholesterol both before and after activation. HDAC3-deficient cells upregulate cholesterol synthesis appropriately after activation, but fail to repress cholesterol efflux; notably, they overexpress cholesterol efflux transporters ABCA1 and ABCG1. Repression of these genes is the primary function for HDAC3 in peripheral CD4+ T cells, as addition of exogenous cholesterol restored proliferative capacity. Collectively, these findings demonstrate HDAC3 is essential during CD4+ T-cell activation to repress cholesterol efflux.Drew WilfahrtRachael L PhilipsJyoti LamaMonika KizerwetterMichael Jeremy ShapiroShaylene A McCueMadeleine M KennedyMatthew J RajculaHu ZengVirginia Smith ShapiroeLife Sciences Publications LtdarticleHDAC3T cell activationcholesterol regulationMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HDAC3 T cell activation cholesterol regulation Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	HDAC3 T cell activation cholesterol regulation Medicine R Science Q Biology (General) QH301-705.5 Drew Wilfahrt Rachael L Philips Jyoti Lama Monika Kizerwetter Michael Jeremy Shapiro Shaylene A McCue Madeleine M Kennedy Matthew J Rajcula Hu Zeng Virginia Smith Shapiro Histone deacetylase 3 represses cholesterol efflux during CD4+ T-cell activation
description	After antigenic activation, quiescent naive CD4+ T cells alter their metabolism to proliferate. This metabolic shift increases production of nucleotides, amino acids, fatty acids, and sterols. Here, we show that histone deacetylase 3 (HDAC3) is critical for activation of murine peripheral CD4+ T cells. HDAC3-deficient CD4+ T cells failed to proliferate and blast after in vitro TCR/CD28 stimulation. Upon T-cell activation, genes involved in cholesterol biosynthesis are upregulated while genes that promote cholesterol efflux are repressed. HDAC3-deficient CD4+ T cells had reduced levels of cellular cholesterol both before and after activation. HDAC3-deficient cells upregulate cholesterol synthesis appropriately after activation, but fail to repress cholesterol efflux; notably, they overexpress cholesterol efflux transporters ABCA1 and ABCG1. Repression of these genes is the primary function for HDAC3 in peripheral CD4+ T cells, as addition of exogenous cholesterol restored proliferative capacity. Collectively, these findings demonstrate HDAC3 is essential during CD4+ T-cell activation to repress cholesterol efflux.
format	article
author	Drew Wilfahrt Rachael L Philips Jyoti Lama Monika Kizerwetter Michael Jeremy Shapiro Shaylene A McCue Madeleine M Kennedy Matthew J Rajcula Hu Zeng Virginia Smith Shapiro
author_facet	Drew Wilfahrt Rachael L Philips Jyoti Lama Monika Kizerwetter Michael Jeremy Shapiro Shaylene A McCue Madeleine M Kennedy Matthew J Rajcula Hu Zeng Virginia Smith Shapiro
author_sort	Drew Wilfahrt
title	Histone deacetylase 3 represses cholesterol efflux during CD4+ T-cell activation
title_short	Histone deacetylase 3 represses cholesterol efflux during CD4+ T-cell activation
title_full	Histone deacetylase 3 represses cholesterol efflux during CD4+ T-cell activation
title_fullStr	Histone deacetylase 3 represses cholesterol efflux during CD4+ T-cell activation
title_full_unstemmed	Histone deacetylase 3 represses cholesterol efflux during CD4+ T-cell activation
title_sort	histone deacetylase 3 represses cholesterol efflux during cd4+ t-cell activation
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/4663fbf5394c4aa88ceec8a8cec5a37d
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Histone deacetylase 3 represses cholesterol efflux during CD4+ T-cell activation

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