Microvascular endothelial cells engulf myelin debris and promote macrophage recruitment and fibrosis after neural injury
Microvascular endothelial cells engulf myelin debris and promote macrophage recruitment and fibrosis after neural injury
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DOI：
10.1038/s41593-018-0324-9
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发表时间：
2019-03-01
影响因子：
25
通讯作者：
Ren, Yi
中科院分区：
文献类型：
--
作者：
Zhou, Tian;Zheng, Yiming;Ren, Yi
受损髓鞘的清除是确保神经损伤后功能恢复的关键。本研究表明，在脊髓损伤（SCI）和实验性自身免疫性脑脊髓炎（EAE）中，微血管及其内层内皮细胞在吞噬髓磷脂碎片中的作用此前未被证实。我们证明了IgG对髓磷脂碎片的调节是内皮细胞有效吞噬髓磷脂碎片所必需的，并且自噬-溶酶体途径对于吞噬髓磷脂碎片的降解至关重要。我们进一步表明，内皮细胞在髓鞘清除之外发挥关键功能，通过调节巨噬细胞浸润、病理性血管生成和纤维化，促进脊髓损伤和EAE中脱髓鞘疾病的进展。出乎意料的是，髓磷脂碎片的吞噬诱导内皮细胞向间质细胞转化，这一过程赋予内皮细胞刺激内皮来源的纤维化成分产生的能力。总的来说，我们的研究表明，髓磷脂碎片通过自噬-溶酶体途径加工促进炎症和血管生成，并可能有助于纤维化疤痕的形成。
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.