Myeloid cells contribute to inflammation and demyelination in the early stages of multiple sclerosis (MS), but it is still unclear to what extent these cells are involved in active lesion formation in progressive MS (PMS). Here, we have harnessed the power of single-cell mass cytometry (CyTOF) to compare myeloid cell phenotypes in active lesions of PMS donors with those in normal-appearing white matter from the same donors and control white matter from non-MS donors. CyTOF measurements of a total of 74 targeted proteins revealed a decreased abundance of homeostatic and TNFhi microglia, and an increase in highly phagocytic and activated microglia states in active lesions of PMS donors. Interestingly, in contrast to results obtained from studies of the inflammatory early disease stages of MS, infiltrating monocyte-derived macrophages were scarce in active lesions of PMS, suggesting fundamental differences of myeloid cell composition in advanced stages of PMS.

中文翻译：

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单细胞质谱流式细胞术揭示了进行性多发性硬化症活动性病变中复杂的骨髓细胞组成。

骨髓细胞在多发性硬化症 (MS) 的早期阶段导致炎症和脱髓鞘，但目前尚不清楚这些细胞在多大程度上参与进行性多发性硬化症 (PMS) 的活动性病变形成。在这里，我们利用单细胞质谱流式细胞术 (CyTOF) 的力量，将 PMS 供体活动性病变中的骨髓细胞表型与来自相同供体的正常白质和非 MS 供体的对照白质中的髓样细胞表型进行比较。CyTOF 对总共 74 种靶蛋白的测量显示，在 PMS 供体的活动性病变中，稳态和 TNFhi 小胶质细胞的丰度减少，而高度吞噬和激活的小胶质细胞状态增加。有趣的是，与多发性硬化症炎症早期阶段的研究结果相反，在经前综合症的活动性病变中，浸润性单核细胞来源的巨噬细胞很少，这表明在经前综合症晚期阶段，骨髓细胞组成存在根本差异。