STING Regulates Peripheral Nerve Regeneration and Colony Stimulating Factor 1 Receptor (CSF1R) Processing in Microglia

Overview

Journal iScience

Publisher Cell Press

Date 2021 Dec 8

PMID 34877494

Citations 3

Authors

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

Affiliations

Soon will be listed here.

Abstract

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 . Taking together, these data highlight a previously unrecognized role of STING in the regulation of nerve regeneration.

Citing Articles

Multilevel analysis of the central-peripheral-target organ pathway: contributing to recovery after peripheral nerve injury.

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