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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Published in:iScience 2021-12, Vol.24 (12), p.103434-103434, Article 103434
Main Authors: 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
Format: Article
Language:English
Subjects:
Cell biology
Immunology
Molecular biology
Neuroscience
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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. [Display omitted] •The cGAS/STING pathway is upregulated in sciatic nerve post nerve injury and in aging•STING ablation increases myelin content and accelerates functional axon recovery•STING KO mice reduces macrophage number in sciatic nerve and microglia activation post injury Molecular biology; Neuroscience; Immunology; Cell biology
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2021.103434