Zinc-dependent histone deacetylases drive neutrophil extracellular trap formation and potentiate local and systemic inflammation

Summary: Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) driven by viruses or bacteria, as well as in numerous immune-mediated disorders. Histone citrullination by the enzyme peptidylarginine deiminase 4 (PAD4) and the cons...

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Autores principales:	Valentina Poli, Victor Pui-Yan Ma, Marco Di Gioia, Achille Broggi, Mehdi Benamar, Qian Chen, Ralph Mazitschek, Stephen J. Haggarty, Talal A. Chatila, Jeffrey M. Karp, Ivan Zanoni
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Molecular biology Immunology Cell biology Functional aspects of cell biology Science Q
Acceso en línea:	https://doaj.org/article/66d5caa429084e78b167076bd43525f3
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spelling	oai:doaj.org-article:66d5caa429084e78b167076bd43525f32021-11-20T05:08:56ZZinc-dependent histone deacetylases drive neutrophil extracellular trap formation and potentiate local and systemic inflammation2589-004210.1016/j.isci.2021.103256https://doaj.org/article/66d5caa429084e78b167076bd43525f32021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012256https://doaj.org/toc/2589-0042Summary: Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) driven by viruses or bacteria, as well as in numerous immune-mediated disorders. Histone citrullination by the enzyme peptidylarginine deiminase 4 (PAD4) and the consequent decondensation of chromatin are hallmarks in the induction of NETs. Nevertheless, additional histone modifications that may govern NETosis are largely overlooked. Herein, we show that histone deacetylases (HDACs) play critical roles in driving NET formation in human and mouse neutrophils. HDACs belonging to the zinc-dependent lysine deacetylases family are necessary to deacetylate histone H3, thus allowing the activity of PAD4 and NETosis. Of note, HDAC inhibition in mice protects against microbial-induced pneumonia and septic shock, decreasing NETosis and inflammation. Collectively, our findings illustrate a new fundamental step that governs the release of NETs and points to HDAC inhibitors as therapeutic agents that may be used to protect against ARDS and sepsis.Valentina PoliVictor Pui-Yan MaMarco Di GioiaAchille BroggiMehdi BenamarQian ChenRalph MazitschekStephen J. HaggartyTalal A. ChatilaJeffrey M. KarpIvan ZanoniElsevierarticleMolecular biologyImmunologyCell biologyFunctional aspects of cell biologyScienceQENiScience, Vol 24, Iss 11, Pp 103256- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Molecular biology Immunology Cell biology Functional aspects of cell biology Science Q
spellingShingle	Molecular biology Immunology Cell biology Functional aspects of cell biology Science Q Valentina Poli Victor Pui-Yan Ma Marco Di Gioia Achille Broggi Mehdi Benamar Qian Chen Ralph Mazitschek Stephen J. Haggarty Talal A. Chatila Jeffrey M. Karp Ivan Zanoni Zinc-dependent histone deacetylases drive neutrophil extracellular trap formation and potentiate local and systemic inflammation
description	Summary: Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) driven by viruses or bacteria, as well as in numerous immune-mediated disorders. Histone citrullination by the enzyme peptidylarginine deiminase 4 (PAD4) and the consequent decondensation of chromatin are hallmarks in the induction of NETs. Nevertheless, additional histone modifications that may govern NETosis are largely overlooked. Herein, we show that histone deacetylases (HDACs) play critical roles in driving NET formation in human and mouse neutrophils. HDACs belonging to the zinc-dependent lysine deacetylases family are necessary to deacetylate histone H3, thus allowing the activity of PAD4 and NETosis. Of note, HDAC inhibition in mice protects against microbial-induced pneumonia and septic shock, decreasing NETosis and inflammation. Collectively, our findings illustrate a new fundamental step that governs the release of NETs and points to HDAC inhibitors as therapeutic agents that may be used to protect against ARDS and sepsis.
format	article
author	Valentina Poli Victor Pui-Yan Ma Marco Di Gioia Achille Broggi Mehdi Benamar Qian Chen Ralph Mazitschek Stephen J. Haggarty Talal A. Chatila Jeffrey M. Karp Ivan Zanoni
author_facet	Valentina Poli Victor Pui-Yan Ma Marco Di Gioia Achille Broggi Mehdi Benamar Qian Chen Ralph Mazitschek Stephen J. Haggarty Talal A. Chatila Jeffrey M. Karp Ivan Zanoni
author_sort	Valentina Poli
title	Zinc-dependent histone deacetylases drive neutrophil extracellular trap formation and potentiate local and systemic inflammation
title_short	Zinc-dependent histone deacetylases drive neutrophil extracellular trap formation and potentiate local and systemic inflammation
title_full	Zinc-dependent histone deacetylases drive neutrophil extracellular trap formation and potentiate local and systemic inflammation
title_fullStr	Zinc-dependent histone deacetylases drive neutrophil extracellular trap formation and potentiate local and systemic inflammation
title_full_unstemmed	Zinc-dependent histone deacetylases drive neutrophil extracellular trap formation and potentiate local and systemic inflammation
title_sort	zinc-dependent histone deacetylases drive neutrophil extracellular trap formation and potentiate local and systemic inflammation
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/66d5caa429084e78b167076bd43525f3
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Zinc-dependent histone deacetylases drive neutrophil extracellular trap formation and potentiate local and systemic inflammation

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