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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number1778
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Simeoli, R., Montague, K., Jones, H. R., Castaldi, L., Chambers, D., Kelleher, J. H., Vacca, V., Pitcher, T., Grist, J., Al-Ahdal, H., Wong, L. F., Perretti, M., Lai, J., Mouritzen, P., Heppenstall, P., & Malcangio, M. (2017). Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma. Nature Communications, 8(1), [1778]. https://doi.org/10.1038/s41467-017-01841-5