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

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-DN...

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Autores principales: Morozzi, Giulio, Rothen, Julian, Toussaint, Gauthier, De Lange, Katrina, Westritschnig, Katrin, Doelemeyer, Arno, Ueberschlag, Vanessa Pitiot, Kahle, Peter, Lambert, Christian, Obrecht, Michael, Beckmann, Nicolau, Ritter, Veronique, Panesar, Moh, Stauffer, Daniela, Garnier, Isabelle, Mueller, Matthias, Guerini, Danilo, Keller, Caroline Gubser, Knehr, Judith, Roma, Guglielmo, Bidinosti, Michael, Brachat, Sophie, Morvan, Frederic, Fornaro, Mara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633968/
https://www.ncbi.nlm.nih.gov/pubmed/34877494
http://dx.doi.org/10.1016/j.isci.2021.103434
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author Morozzi, Giulio
Rothen, Julian
Toussaint, Gauthier
De Lange, Katrina
Westritschnig, Katrin
Doelemeyer, Arno
Ueberschlag, Vanessa Pitiot
Kahle, Peter
Lambert, Christian
Obrecht, Michael
Beckmann, Nicolau
Ritter, Veronique
Panesar, Moh
Stauffer, Daniela
Garnier, Isabelle
Mueller, Matthias
Guerini, Danilo
Keller, Caroline Gubser
Knehr, Judith
Roma, Guglielmo
Bidinosti, Michael
Brachat, Sophie
Morvan, Frederic
Fornaro, Mara
author_facet Morozzi, Giulio
Rothen, Julian
Toussaint, Gauthier
De Lange, Katrina
Westritschnig, Katrin
Doelemeyer, Arno
Ueberschlag, Vanessa Pitiot
Kahle, Peter
Lambert, Christian
Obrecht, Michael
Beckmann, Nicolau
Ritter, Veronique
Panesar, Moh
Stauffer, Daniela
Garnier, Isabelle
Mueller, Matthias
Guerini, Danilo
Keller, Caroline Gubser
Knehr, Judith
Roma, Guglielmo
Bidinosti, Michael
Brachat, Sophie
Morvan, Frederic
Fornaro, Mara
author_sort Morozzi, Giulio
collection PubMed
description 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.
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spelling pubmed-86339682021-12-06 STING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia Morozzi, Giulio Rothen, Julian Toussaint, Gauthier De Lange, Katrina Westritschnig, Katrin Doelemeyer, Arno Ueberschlag, Vanessa Pitiot Kahle, Peter Lambert, Christian Obrecht, Michael Beckmann, Nicolau Ritter, Veronique Panesar, Moh Stauffer, Daniela Garnier, Isabelle Mueller, Matthias Guerini, Danilo Keller, Caroline Gubser Knehr, Judith Roma, Guglielmo Bidinosti, Michael Brachat, Sophie Morvan, Frederic Fornaro, Mara iScience Article 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. Elsevier 2021-11-14 /pmc/articles/PMC8633968/ /pubmed/34877494 http://dx.doi.org/10.1016/j.isci.2021.103434 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Morozzi, Giulio
Rothen, Julian
Toussaint, Gauthier
De Lange, Katrina
Westritschnig, Katrin
Doelemeyer, Arno
Ueberschlag, Vanessa Pitiot
Kahle, Peter
Lambert, Christian
Obrecht, Michael
Beckmann, Nicolau
Ritter, Veronique
Panesar, Moh
Stauffer, Daniela
Garnier, Isabelle
Mueller, Matthias
Guerini, Danilo
Keller, Caroline Gubser
Knehr, Judith
Roma, Guglielmo
Bidinosti, Michael
Brachat, Sophie
Morvan, Frederic
Fornaro, Mara
STING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633968/
https://www.ncbi.nlm.nih.gov/pubmed/34877494
http://dx.doi.org/10.1016/j.isci.2021.103434
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