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

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Raffaele Simeoli, Karli Montague, Hefin R. Jones, Laura Castaldi, David Chambers, Jayne H. Kelleher, Valentina Vacca, Thomas Pitcher, John Grist, Hadil Al-Ahdal, Liang-Fong Wong, Mauro Perretti, Johnathan Lai, Peter Mouritzen, Paul Heppenstall, Marzia Malcangio

Original languageEnglish
Pages (from-to)1778
Number of pages1
JournalNature Communications
Issue number1
Early online date24 Nov 2017
Accepted/In press20 Oct 2017
E-pub ahead of print24 Nov 2017
Published24 Nov 2017


King's Authors


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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