Exosomal USP13 derived from microvascular endothelial cells regulates immune microenvironment and improves functional recovery after spinal cord injury by stabilizing IκBα

Spinal cord injury (SCI) often leads to permanent loss of movement and sensation, and current treatments are limited. This study investigates how vascular endothelial cells, which line blood vessels, communicate with immune cells (microglia and macrophages) after SCI. The researchers found that exosomes, tiny vesicles released by these endothelial cells, can promote the polarization of microglia and macrophages towards an anti-inflammatory (M2) phenotype. This shift reduces inflammation and supports nerve regeneration in the injured spinal cord. Specifically, the study identifies a protein called USP13 within these exosomes as a key player. USP13 stabilizes IκBα, a protein that inhibits the NF-κB signaling pathway, thereby reducing inflammation and promoting recovery after SCI.

• 1
  Exosomes derived from microvascular endothelial cells promote motor rehabilitation and M2 polarization of microglia/macrophages after SCI.
• 2
  Exosomal USP13 regulates microglia/macrophages polarization after SCI by stabilizing IκBα, thus inhibiting the NF-κB signaling pathway.
• 3
  Administration of the selective IκBα inhibitor betulinic acid (BA) inhibited the beneficial effect of Exos in vivo.