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

Author

Listed:
  • Raffaele Simeoli

    (King’s College London)

  • Karli Montague

    (King’s College London)

  • Hefin R. Jones

    (Barts and The London School of Medicine, Queen Mary University of London)

  • Laura Castaldi

    (EMBL Monterotondo)

  • David Chambers

    (King’s College London)

  • Jayne H. Kelleher

    (King’s College London)

  • Valentina Vacca

    (King’s College London
    National Research Council and IRCCS Fondazione Santa Lucia)

  • Thomas Pitcher

    (King’s College London)

  • John Grist

    (King’s College London)

  • Hadil Al-Ahdal

    (Medical Science Building, University of Bristol)

  • Liang-Fong Wong

    (Medical Science Building, University of Bristol)

  • Mauro Perretti

    (Barts and The London School of Medicine, Queen Mary University of London)

  • Johnathan Lai

    (Exiqon A/S)

  • Peter Mouritzen

    (Exiqon A/S)

  • Paul Heppenstall

    (EMBL Monterotondo)

  • Marzia Malcangio

    (King’s College London)

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.

Suggested Citation

  • 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 Perr, 2017. "Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01841-5
    DOI: 10.1038/s41467-017-01841-5
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    Cited by:

    1. Shambhu Yadav & Markus Waldeck-Weiermair & Fotios Spyropoulos & Roderick Bronson & Arvind K. Pandey & Apabrita Ayan Das & Alexander C. Sisti & Taylor A. Covington & Venkata Thulabandu & Shari Caplan &, 2023. "Sensory ataxia and cardiac hypertrophy caused by neurovascular oxidative stress in chemogenetic transgenic mouse lines," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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