Infiltrating monocyte-derived macrophages polarizes in to anti-inflammatory and neuro-protective phenotype in a rat model of cerebral ischemia

To summarize our results, we found microglia and MDMs are functionally heterogeneous population contributing differently to the disease phenotype. Our data, suggest that during post-ischemic inflammation microglia exhibit pro-inflammatory phenotype, while infiltrating MDMs display anti-inflammatory and neuro-protective phenotype. Apart from up-regulation of some of the classical M2 marker in MDMs, our gene expression profiling using RNA-sequencing revealed a unique signature of MDMs with the up-regulation of genes associated with wound healing, MHCII antigen-presentation and tissue repair. Our results strongly suggest that MDMs infiltrating the CNS parenchyma during the sub-acute of post-ischemic inflammation might contribute to the endogenous mechanism of neuroprotection.为总结本研究成果，我们发现小胶质细胞（microglia）与单核细胞衍生巨噬细胞（monocyte-derived macrophages, MDMs）属于功能异质性群体，二者对疾病表型的贡献存在显著差异。研究数据表明，在缺血后炎症进程中，小胶质细胞呈现促炎表型，而浸润性单核细胞衍生巨噬细胞则表现为抗炎与神经保护表型。除单核细胞衍生巨噬细胞内部分经典M2型标志物发生上调外，我们通过RNA测序（RNA-sequencing）开展的基因表达谱分析显示，该类细胞存在独特的基因表达特征：其与伤口愈合、MHCII类抗原呈递及组织修复相关的基因均呈现上调趋势。本研究结果有力提示，在缺血后炎症亚急性期浸润中枢神经系统实质（CNS parenchyma）的单核细胞衍生巨噬细胞，可能参与内源性神经保护的调控机制。