STING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia

Summary: Inflammatory responses are crucial for regeneration following peripheral nerve injury (PNI). PNI triggers inflammatory responses at the site of injury. The DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) and its downstream effector stimulator of interferon genes (STING) sense foreign an...

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Autores principales:	Giulio Morozzi, Julian Rothen, Gauthier Toussaint, Katrina De Lange, Katrin Westritschnig, Arno Doelemeyer, Vanessa Pitiot Ueberschlag, Peter Kahle, Christian Lambert, Michael Obrecht, Nicolau Beckmann, Veronique Ritter, Moh Panesar, Daniela Stauffer, Isabelle Garnier, Matthias Mueller, Danilo Guerini, Caroline Gubser Keller, Judith Knehr, Guglielmo Roma, Michael Bidinosti, Sophie Brachat, Frederic Morvan, Mara Fornaro
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Molecular biology Neuroscience Immunology Cell biology Science Q
Acceso en línea:	https://doaj.org/article/34f8e9f03cac483cb7ab6b1f71128e9e
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spelling	oai:doaj.org-article:34f8e9f03cac483cb7ab6b1f71128e9e2021-11-28T04:36:20ZSTING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia2589-004210.1016/j.isci.2021.103434https://doaj.org/article/34f8e9f03cac483cb7ab6b1f71128e9e2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S258900422101405Xhttps://doaj.org/toc/2589-0042Summary: Inflammatory responses are crucial for regeneration following peripheral nerve injury (PNI). PNI triggers inflammatory responses at the site of injury. The DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) and its downstream effector stimulator of interferon genes (STING) sense foreign and self-DNA and trigger type I interferon (IFN) immune responses. We demonstrate here that following PNI, the cGAS/STING pathway is upregulated in the sciatic nerve of naive rats and dysregulated in old rats. In a nerve crush mouse model where STING is knocked out, myelin content in sciatic nerve is increased resulting in accelerated functional axon recovery. STING KO mice have lower macrophage number in sciatic nerve and decreased microglia activation in spinal cord 1 week post injury. STING activation regulated processing of colony stimulating factor 1 receptor (CSF1R) and microglia survival in vitro. Taking together, these data highlight a previously unrecognized role of STING in the regulation of nerve regeneration.Giulio MorozziJulian RothenGauthier ToussaintKatrina De LangeKatrin WestritschnigArno DoelemeyerVanessa Pitiot UeberschlagPeter KahleChristian LambertMichael ObrechtNicolau BeckmannVeronique RitterMoh PanesarDaniela StaufferIsabelle GarnierMatthias MuellerDanilo GueriniCaroline Gubser KellerJudith KnehrGuglielmo RomaMichael BidinostiSophie BrachatFrederic MorvanMara FornaroElsevierarticleMolecular biologyNeuroscienceImmunologyCell biologyScienceQENiScience, Vol 24, Iss 12, Pp 103434- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Molecular biology Neuroscience Immunology Cell biology Science Q
spellingShingle	Molecular biology Neuroscience Immunology Cell biology Science Q Giulio Morozzi Julian Rothen Gauthier Toussaint Katrina De Lange Katrin Westritschnig Arno Doelemeyer Vanessa Pitiot Ueberschlag Peter Kahle Christian Lambert Michael Obrecht Nicolau Beckmann Veronique Ritter Moh Panesar Daniela Stauffer Isabelle Garnier Matthias Mueller Danilo Guerini Caroline Gubser Keller Judith Knehr Guglielmo Roma Michael Bidinosti Sophie Brachat Frederic Morvan Mara Fornaro STING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia
description	Summary: Inflammatory responses are crucial for regeneration following peripheral nerve injury (PNI). PNI triggers inflammatory responses at the site of injury. The DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) and its downstream effector stimulator of interferon genes (STING) sense foreign and self-DNA and trigger type I interferon (IFN) immune responses. We demonstrate here that following PNI, the cGAS/STING pathway is upregulated in the sciatic nerve of naive rats and dysregulated in old rats. In a nerve crush mouse model where STING is knocked out, myelin content in sciatic nerve is increased resulting in accelerated functional axon recovery. STING KO mice have lower macrophage number in sciatic nerve and decreased microglia activation in spinal cord 1 week post injury. STING activation regulated processing of colony stimulating factor 1 receptor (CSF1R) and microglia survival in vitro. Taking together, these data highlight a previously unrecognized role of STING in the regulation of nerve regeneration.
format	article
author	Giulio Morozzi Julian Rothen Gauthier Toussaint Katrina De Lange Katrin Westritschnig Arno Doelemeyer Vanessa Pitiot Ueberschlag Peter Kahle Christian Lambert Michael Obrecht Nicolau Beckmann Veronique Ritter Moh Panesar Daniela Stauffer Isabelle Garnier Matthias Mueller Danilo Guerini Caroline Gubser Keller Judith Knehr Guglielmo Roma Michael Bidinosti Sophie Brachat Frederic Morvan Mara Fornaro
author_facet	Giulio Morozzi Julian Rothen Gauthier Toussaint Katrina De Lange Katrin Westritschnig Arno Doelemeyer Vanessa Pitiot Ueberschlag Peter Kahle Christian Lambert Michael Obrecht Nicolau Beckmann Veronique Ritter Moh Panesar Daniela Stauffer Isabelle Garnier Matthias Mueller Danilo Guerini Caroline Gubser Keller Judith Knehr Guglielmo Roma Michael Bidinosti Sophie Brachat Frederic Morvan Mara Fornaro
author_sort	Giulio Morozzi
title	STING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia
title_short	STING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia
title_full	STING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia
title_fullStr	STING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia
title_full_unstemmed	STING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia
title_sort	sting regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (csf1r) processing in microglia
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/34f8e9f03cac483cb7ab6b1f71128e9e
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STING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia

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