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Nat Commun. 2017 Nov 24;8(1):1778. doi: 10.1038/s41467-017-01841-5.

Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma.

Author information

1
Wolfson Centre for Age Related Diseases, King's College London, London, SE1 1UL, UK.
2
The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, EC1M 6BQ, UK.
3
EMBL Monterotondo, Via Ramarini 32, 00016, Monterotondo, Italy.
4
Institute of Cell Biology and Neurobiology, National Research Council and IRCCS Fondazione Santa Lucia, 00143, Rome, Italy.
5
School of Clinical Sciences, Medical Science Building, University of Bristol, Bristol, BS8 1TD, UK.
6
Exiqon A/S, Skelstedet 16, 2950, Vedbaek, Denmark.
7
Wolfson Centre for Age Related Diseases, King's College London, London, SE1 1UL, UK. marzia.malcangio@kcl.ac.uk.

Abstract

Following peripheral axon injury, dysregulation of non-coding microRNAs (miRs) occurs in dorsal root ganglia (DRG) sensory neurons. Here we show that DRG neuron cell bodies release extracellular vesicles, including exosomes containing miRs, upon activity. We demonstrate that miR-21-5p is released in the exosomal fraction of cultured DRG following capsaicin activation of TRPV1 receptors. Pure sensory neuron-derived exosomes released by capsaicin are readily phagocytosed by macrophages in which an increase in miR-21-5p expression promotes a pro-inflammatory phenotype. After nerve injury in mice, miR-21-5p is upregulated in DRG neurons and both intrathecal delivery of a miR-21-5p antagomir and conditional deletion of miR-21 in sensory neurons reduce neuropathic hypersensitivity as well as the extent of inflammatory macrophage recruitment in the DRG. We suggest that upregulation and release of miR-21 contribute to sensory neuron-macrophage communication after damage to the peripheral nerve.

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