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

in Publications November 30, 2017

Following peripheral axon injury, dysregulation of non-coding microRNAs (miRs) occurs in dorsal root ganglia (DRG) sensory neurons. Researchers from King’s College London show that DRG neuron cell bodies release extracellular vesicles, including exosomes containing miRs, upon activity. They 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. The researchers suggest that upregulation and release of miR-21 contribute to sensory neuron-macrophage communication after damage to the peripheral nerve.

Exosomes released from pure sensory neurons after capsaicin are
phagocytosed by macrophages

a, b Representative scatterplots (gating strategy) and ImageStream^TM images showing EVs (CFSE-labeled, green) uptake by macrophages (F4/80⁺, red). EVs were isolated from culture media after incubation of pure DRG neurons with buffer control or CAPS for 3 h. c Percentage-positive and median fluorescence intensity of CFSE⁺ macrophages incubated with neuron-derived EVs. Data are means ± S.E.M., n = 4. *P < 0.05, compared to control, Student’s t-test. d Nos2, Mrc1, and Spry2 mRNA expression levels in macrophages incubated with and without exosomes derived from CAPS-treated pure DRG neurons. e Nos2 and Spry2 mRNA expression levels in macrophages transfected with miR-21-5p antagomir or scrambled oligomer and incubated with EVs derived from CAPS-treated pure DRG neurons. Data are means ± S.E.M., n = 3; *P < 0.05 and **P < 0.01 Student’s t-test

Simeoli R, Montague K, Jones HR, Castaldi L, Chambers D, Kelleher JH, Vacca V, Pitcher T, Grist J, Al-Ahdal H, Wong LF, Perretti M, Lai J, Mouritzen P, Heppenstall P, Malcangio M. (2017) Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma. Nat Commun 8(1):1778. [article]