Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool
Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool
复制标题
DOI：
10.1038/nn.2887
复制
发表时间：
2011-09-01
影响因子：
25
通讯作者：
Rossi, Fabio M. V.
中科院分区：
文献类型：
--
作者：
Ajami, Bahareh;Bennett, Jami L.;Rossi, Fabio M. V.
在多发性硬化症和实验性自身免疫性脑炎（EAE）小鼠模型中，两个形态学上无法区分的吞噬细胞池，小胶质细胞和炎性巨噬细胞，分别来自增殖的常驻前体细胞和血源性祖细胞的募集。这些细胞类型是否在功能上等同是激烈争论的，但在实验上解决是具有挑战性的。我们使用共生和骨髓消融相结合来替代循环祖细胞而不影响中枢神经系统驻留的小胶质细胞，发现单核细胞浸润与EAE进展至麻痹阶段之间存在强相关性。抑制趋化因子受体依赖的单核细胞向中枢神经系统的募集阻断了EAE的进展，表明这些浸润细胞是发病机制所必需的。最后，我们发现，虽然小胶质细胞可以进入细胞周期并在缓解后恢复到静止状态，但募集的单核细胞消失，因此最终不会对驻留的小胶质细胞库做出贡献。总之，我们确定了两个不同的亚群的骨髓单核细胞在神经炎症和疾病进展的不同作用。
In multiple sclerosis and the experimental autoimmune encephalitis (EAE) mouse model, two pools of morphologically indistinguishable phagocytic cells, microglia and inflammatory macrophages, accrue from proliferating resident precursors and recruitment of blood-borne progenitors, respectively. Whether these cell types are functionally equivalent is hotly debated, but is challenging to address experimentally. Using a combination of parabiosis and myeloablation to replace circulating progenitors without affecting CNS-resident microglia, we found a strong correlation between monocyte infiltration and progression to the paralytic stage of EAE. Inhibition of chemokine receptor-dependent recruitment of monocytes to the CNS blocked EAE progression, suggesting that these infiltrating cells are essential for pathogenesis. Finally, we found that, although microglia can enter the cell cycle and return to quiescence following remission, recruited monocytes vanish, and therefore do not ultimately contribute to the resident microglial pool. In conclusion, we identified two distinct subsets of myelomonocytic cells with distinct roles in neuroinflammation and disease progression.