Microglia and macrophages promote corralling, wound compaction and recovery after spinal cord injury via Plexin-B2

Microglia and macrophages promote corralling, wound compaction and recovery after spinal cord injury via Plexin-B2
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小胶质细胞和巨噬细胞通过 Plexin-B2 促进脊髓损伤后的聚集、伤口压实和恢复

DOI:
10.1038/s41593-020-0597-7
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发表时间:
2020-02
影响因子:
25
通讯作者:
Hongyan Zou
Hongyan Zou
中科院分区:
医学1区
文献类型:
--
作者:
Xiang Zhou;Shalaka Wahane;Marie-Sophie Friedl;Michael Kluge;Caroline C.Friedel;Kleopatra Avrampou;Venetia Zachariou;Lei Guo;Bin Zhang;Xijing He;Rol;H.Friedel;Hongyan Zou

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脊髓损伤后的组织修复需要动员免疫细胞和神经胶质细胞形成保护屏障,密封伤口,促进碎片清除、炎症遏制和基质压实。这个过程包括围捕,其中吞噬免疫细胞被限制在坏死核心,坏死核心被星形细胞边界包围。在这里,我们阐明了在损伤激活的小胶质细胞和巨噬细胞(iam)中参与轴突引导通路的一个暂时不同的基因特征。神经丛蛋白b2在iam中上调,是脊髓损伤后运动感觉恢复所必需的。髓系细胞中的丛蛋白b2缺失会损害聚集,导致弥漫性组织损伤、炎症外溢和轴突再生受阻。在小胶质细胞和巨噬细胞中,聚集开始得很早,需要丛蛋白b2。从机制上讲,丛状蛋白b2促进小胶质细胞的运动,引导内酰胺远离碰撞细胞,促进基质压实。因此,我们的数据表明,在伤口愈合过程中,Plexin-B2是整合iam与损伤微环境的生化信号和物理相互作用的重要环节。
Tissue repair after spinal cord injury requires the mobilization of immune and glial cells to form a protective barrier that seals the wound and facilitates debris clearing, inflammatory containment and matrix compaction. This process involves corralling, wherein phagocytic immune cells become confined to the necrotic core, which is surrounded by an astrocytic border. Here we elucidate a temporally distinct gene signature in injury-activated microglia and macrophages (IAMs) that engages axon guidance pathways. Plexin-B2 is upregulated in IAMs and is required for motor sensory recovery after spinal cord injury. Plexin-B2 deletion in myeloid cells impairs corralling, leading to diffuse tissue damage, inflammatory spillover and hampered axon regeneration. Corralling begins early and requires Plexin-B2 in both microglia and macrophages. Mechanistically, Plexin-B2 promotes microglia motility, steers IAMs away from colliding cells and facilitates matrix compaction. Our data therefore establish Plexin-B2 as an important link that integrates biochemical cues and physical interactions of IAMs with the injury microenvironment during wound healing.
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