Activation Status of Human Microglia Is Dependent on Lesion Formation Stage and Remyelination in Multiple Sclerosis
Activation Status of Human Microglia Is Dependent on Lesion Formation Stage and Remyelination in Multiple Sclerosis
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DOI：
10.1097/nen.0000000000000149
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发表时间：
2015-01-01
影响因子：
3.2
通讯作者：
Amor, Sandra
中科院分区：
文献类型：
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作者：
Peferoen, Laura A. N.;Vogel, Daphne Y. S.;Amor, Sandra
与巨噬细胞类似，小胶质细胞采用不同的激活状态，有助于多发性硬化症的修复和组织损伤。利用逆转录定量聚合酶链反应和免疫组织化学，我们发现体外 M1 极化（促炎）成人小胶质细胞表达独特的标记物 CD74、CD40、CD86 和 CCR7，而 M2（抗炎）小胶质细胞表达甘露糖受体和抗炎细胞因子 CCL22。这些标记物的表达在正常白质（活动前病变）和髓鞘再生区域（代表修复性多发性硬化症病变）的激活小胶质细胞簇中进行评估。我们发现，活动前和髓鞘再生病变中激活的小胶质细胞表达 CD74、CD40、CD86 以及 M2 标记物 CCL22 和 CD209，但不表达甘露糖受体。为了检查这种中间小胶质细胞特征是静态的还是动态的，从而容易受到微环境变化的影响，我们在体外将小胶质细胞极化为 M1 或 M2 表型，然后用相反的极化方案对其进行处理。这些研究表明，CD40、CXCL10 和甘露糖受体的表达是动态的，并且小胶质细胞与巨噬细胞一样，可以在 M1 和 M2 表型特征之间切换。综上所述，我们的数据定义了受多发性硬化症影响的中枢神经系统组织病变发展过程中小胶质细胞的差异激活状态，并强调了人类成年小胶质细胞的体外可塑性。
Similar to macrophages, microglia adopt diverse activation states and contribute to repair and tissue damage in multiple sclerosis. Using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, we show that in vitro M1-polarized (proinflammatory) human adult microglia express the distinctive markers CD74, CD40, CD86, and CCR7, whereas M2 (anti-inflammatory) microglia express mannose receptor and the anti-inflammatory cytokine CCL22. The expression of these markers was assessed in clusters of activated microglia in normal-appearing white matter (preactive lesions) and areas of remyelination, representing reparative multiple sclerosis lesions. We show that activated microglia in preactive and remyelinating lesions express CD74, CD40, CD86, and the M2 markers CCL22 and CD209, but not mannose receptor. To examine whether this intermediate microglia profile is static or dynamic and thus susceptible to changes in the microenvironment, we polarized microglia into M1 or M2 phenotype in vitro and then subsequently treated them with the opposing polarization regimen. These studies revealed that expression of CD40, CXCL10, and mannose receptor is dynamic and that microglia, like macrophages, can switch between M1 and M2 phenotypic profiles. Taken together, our data define the differential activation states of microglia during lesion development in multiple sclerosis-affected CNS tissues and underscore the plasticity of human adult microglia in vitro.