Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Nat Neurosci. 2020 Mar;23(3):337-350. doi: 10.1038/s41593-020-0597-7.
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.
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，以封闭伤口，促进碎片清除、炎症控制和基质压实。这个过程涉及到吞噬细胞的募集，其中吞噬免疫细胞被局限在坏死核心内，而坏死核心被星形胶质细胞边界包围。在这里，我们阐明了在损伤激活的小胶质细胞和巨噬细胞（IAMs）中具有时间上不同的基因特征，该特征涉及轴突导向途径。Plexin-B2 在 IAMs 中上调，并且在脊髓损伤后运动感觉恢复中是必需的。髓系细胞中 Plexin-B2 的缺失会损害募集作用，导致弥漫性组织损伤、炎症溢出和轴突再生受阻。募集作用很早就开始，并需要小胶质细胞和巨噬细胞中的 Plexin-B2。从机制上讲，Plexin-B2 促进小胶质细胞的迁移，引导 IAMs 远离碰撞细胞，并促进基质压实。因此，我们的数据将 Plexin-B2 确立为一个重要的联系，它整合了 IAMs 的生化线索和物理相互作用，以及在伤口愈合过程中损伤微环境的关系。
