Microvascular endothelial cells engulf myelin debris and promote macrophage recruitment and fibrosis after neural injury

The study identifies a novel role for microvessels and their endothelial cells in clearing myelin debris following spinal cord injury (SCI) and experimental autoimmune encephalomyelitis (EAE). These cells engulf myelin, a process requiring IgG opsonization and the autophagy-lysosome pathway for degradation. Beyond clearance, endothelial cells contribute to disease progression by modulating macrophage infiltration, pathological angiogenesis, and fibrosis. Myelin debris engulfment triggers endothelial-to-mesenchymal transition (EndoMT), enabling endothelial cells to produce fibrotic components. The research reveals that processing myelin debris through the autophagy-lysosome pathway fosters inflammation and angiogenesis, potentially leading to fibrotic scar formation. These processes are all closely associated with CNS demyelinating disorders.

• 1
  Microvascular endothelial cells act as amateur phagocytes to engulf myelin debris in SCI and EAE, requiring IgG opsonization for effective uptake.
• 2
  The autophagy-lysosome pathway is essential for the degradation of engulfed myelin debris within endothelial cells, and this process is linked to pro-angiogenic, pro-inflammatory, and pro-fibrotic responses.
• 3
  Endothelial cell engulfment of myelin debris induces endothelial-to-mesenchymal transition (EndoMT), leading to the production of fibrotic components and contributing to fibrotic scar formation in demyelinated regions.