Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease
Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease
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DOI：
10.1182/blood-2008-07-168575
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发表时间：
2009-04-02
期刊：
影响因子：
20.3
通讯作者：
Segal, Benjamin M.
中科院分区：
文献类型：
--
作者：
King, Irah L.;Dickendesher, Travis L.;Segal, Benjamin M.
成熟的髓系细胞（巨噬细胞和CD11b⁺树突状细胞）是多发性硬化症和实验性自身免疫性脑脊髓炎（EAE）中神经炎症浸润的重要组成部分。在复发和慢性神经炎症期间这些细胞是如何补充的机制尚不清楚。在此我们证明，具有集落形成潜能的CD11b⁺CD62L⁺Ly6C⁺单核细胞在EAE复发前夕通过粒细胞 - 巨噬细胞集落刺激因子依赖的途径被动员到血液中。循环中的Ly6C⁺单核细胞穿过血脑屏障，上调促炎分子，并分化为中枢神经系统树突状细胞和巨噬细胞。循环池中Ly6C⁺单核细胞的富集与临床EAE的发病更早和严重程度增加有关。我们的研究表明，粒细胞 - 巨噬细胞集落刺激因子驱动的Ly6C⁺前体细胞从骨髓释放，可防止在复发或慢性自身免疫性脱髓鞘过程中中枢神经系统髓系细胞群耗竭，这提示了一个新的治疗靶向途径。（《血液》2009年；113卷：3190 - 3197页）
Mature myeloid cells (macrophages and CD11b(+) dendritic cells) form a prominent component of neuroinflammatory infiltrates in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). The mechanism by which these cells are replenished during relapsing and chronic neuroinflammation is poorly understood. Here we demonstrate that CD11b(+)CD62L(+)Ly6C(hi) monocytes with colony-forming potential are mobilized into the bloodstream by a granulocyte-macrophage colony-stimulating factor-dependent pathway immediately before EAE relapses. Circulating Ly6C(hi) monocytes traffic across the blood-brain barrier, up-regulate proinflammatory molecules, and differentiate into central nervous system dendritic cells and macrophages. Enrichment of Ly6Chi monocytes in the circulating pool is associated with an earlier onset and increased severity of clinical EAE. Our studies indicate that granulocyte-macrophage colony-stimulating factor-driven release of Ly6Chi precursors from the bone marrow prevents exhaustion of central nervous system myeloid populations during relapsing or chronic autoimmune demyelination, suggesting a novel pathway for therapeutic targeting. (Blood. 2009; 113:3190-3197)