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

Tian Zhou, Yiming Zheng, Li Sun, Smaranda Ruxandra Badea, Yuanhu Jin, Yang Liu, Alyssa J. Rolfe, Haitao Sun, Xi Wang, Zhijian Cheng, Zhaoshuai Huang, Na Zhao, Xin Sun, Jinhua Li, Jianqing Fan, Choogon Lee, Timothy L. Megraw, Wutian Wu, Guixue Wang, Yi Ren

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The clearance of damaged myelin sheaths is critical to ensure functional recovery from neural injury. Here we show a previously unidentified role for microvessels and their lining endothelial cells in engulfing myelin debris in spinal cord injury (SCI) and experimental autoimmune encephalomyelitis (EAE). We demonstrate that IgG opsonization of myelin debris is required for its effective engulfment by endothelial cells and that the autophagy–lysosome pathway is crucial for degradation of engulfed myelin debris. We further show that endothelial cells exert critical functions beyond myelin clearance to promote progression of demyelination disorders by regulating macrophage infiltration, pathologic angiogenesis and fibrosis in both SCI and EAE. Unexpectedly, myelin debris engulfment induces endothelial-to-mesenchymal transition, a process that confers upon endothelial cells the ability to stimulate the endothelial-derived production of fibrotic components. Overall, our study demonstrates that the processing of myelin debris through the autophagy–lysosome pathway promotes inflammation and angiogenesis and may contribute to fibrotic scar formation.

Original languageEnglish (US)
Pages (from-to)421-435
Number of pages15
JournalNature neuroscience
Volume22
Issue number3
DOIs
StatePublished - Mar 1 2019

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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