Mononuclear phagocytes locally specify and adapt their phenotype in a multiple sclerosis model
Mononuclear phagocytes locally specify and adapt their phenotype in a multiple sclerosis model
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DOI：
10.1038/s41593-018-0212-3
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发表时间：
2018-09-01
影响因子：
25
通讯作者：
Kerschensteiner, Martin
中科院分区：
文献类型：
--
作者：
Locatelli, Giuseppe;Theodorou, Delphine;Kerschensteiner, Martin
单核巨噬细胞是神经炎症性疾病如多发性硬化症中组织损伤和修复的关键调节因子。为了研究炎症中枢神经系统中不同的吞噬细胞表型，我们引入了一种体内成像方法，使我们能够在时间和空间上解决多发性硬化症小鼠模型中吞噬细胞极化的演变。我们发现，最初的促炎性极化的吞噬细胞建立后，脊髓入境，并严重依赖于他们进入的车厢。在中枢神经系统环境信号的引导下，单个吞噬细胞随着病变从扩张到消退而改变其表型。因此，我们的研究提供了一个实时分析的时空决定因素和监管原则的吞噬细胞规格在发炎的中枢神经系统。
Mononuclear phagocytes are key regulators of both tissue damage and repair in neuroinflammatory conditions such as multiple sclerosis. To examine divergent phagocyte phenotypes in the inflamed CNS, we introduce an in vivo imaging approach that allows us to temporally and spatially resolve the evolution of phagocyte polarization in a murine model of multiple sclerosis. We show that the initial proinflammatory polarization of phagocytes is established after spinal cord entry and critically depends on the compartment they enter. Guided by signals from the CNS environment, individual phagocytes then switch their phenotype as lesions move from expansion to resolution. Our study thus provides a real-time analysis of the temporospatial determinants and regulatory principles of phagocyte specification in the inflamed CNS.