Spinal cord injury causes chronic bone marrow failure
Spinal cord injury causes chronic bone marrow failure
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DOI：
10.1038/s41467-020-17564-z
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发表时间：
2020-07-24
影响因子：
16.6
通讯作者：
Popovich, Phillip G.
中科院分区：
文献类型：
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作者：
Carpenter, Randall S.;Marbourg, Jessica M.;Popovich, Phillip G.
脊髓损伤（SCI）导致免疫功能障碍，增加感染性发病率和死亡率的风险。由于骨髓造血对正常的免疫功能是必不可少的，我们假设SCI破坏了骨髓造血。事实上，SCI导致骨髓造血干细胞和祖细胞（HSPC）过度增殖，但这些细胞不能离开骨髓，即使在用强有力的炎症刺激物挑战宿主之后。SCI后骨髓中HSPC的隔离与异常趋化性信号传导有关，可通过损伤后注射Plerixafor（AMD3100）（一种CXCR4的小分子抑制剂）逆转。即使普乐沙福从骨髓中释放HSPC和成熟免疫细胞，竞争性再增殖试验表明，SCI小鼠中HSPC的内在长期功能能力仍然受损。总之，我们的数据表明，脊髓损伤导致获得性骨髓衰竭综合征，可能有助于慢性免疫功能障碍。脊髓损伤（SCI）通常会导致免疫功能障碍，但仍然缺乏机制见解。在这里，作者表明SCI改变了趋化因子信号传导，并诱导造血干细胞和祖细胞迁移的长期持续缺陷，从而将它们困在骨髓中并破坏外周免疫稳态。
Spinal cord injury (SCI) causes immune dysfunction, increasing the risk of infectious morbidity and mortality. Since bone marrow hematopoiesis is essential for proper immune function, we hypothesize that SCI disrupts bone marrow hematopoiesis. Indeed, SCI causes excessive proliferation of bone marrow hematopoietic stem and progenitor cells (HSPC), but these cells cannot leave the bone marrow, even after challenging the host with a potent inflammatory stimulus. Sequestration of HSPCs in bone marrow after SCI is linked to aberrant chemotactic signaling that can be reversed by post-injury injections of Plerixafor (AMD3100), a small molecule inhibitor of CXCR4. Even though Plerixafor liberates HSPCs and mature immune cells from bone marrow, competitive repopulation assays show that the intrinsic long-term functional capacity of HSPCs is still impaired in SCI mice. Together, our data suggest that SCI causes an acquired bone marrow failure syndrome that may contribute to chronic immune dysfunction. Spinal cord injury (SCI) often leads to immune dysfunction, but mechanistic insights are still lacking. Here the authors show that SCI alters chemokine signaling and induces long, persisting defects in hematopoietic stem and progenitor cell migration, thereby entrapping them in the bone marrow and disrupting peripheral immune homeostasis.