Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration
Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration
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DOI：
10.1038/s41590-019-0356-7
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发表时间：
2019-05-01
影响因子：
30.5
通讯作者：
Nagy, Laszlo
中科院分区：
文献类型：
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作者：
Giannakis, Nikolas;Sansbury, Brian E.;Nagy, Laszlo
肌肉损伤激发无菌免疫反应，促进完全再生。在这里，我们使用基于质谱的脂质组学来绘制骨骼肌损伤从炎症到消退和再生的过渡过程中的介质脂质组。我们观察到时间调节甘油磷脂和生产的促炎性脂质介质（例如，白三烯和白藜芦醇）和专门的前解决脂质介质（例如，resolvins和脂氧素），布洛芬调制。这些时间依赖性特征在分选的中性粒细胞和Ly6C（hi）和Ly6C（lo）肌肉浸润性巨噬细胞中重现，在Ly6C（lo）巨噬细胞中观察到明显的促消退特征。用消退素D2刺激的巨噬细胞的RNA测序显示出与从Ly6C（hi）巨噬细胞到Ly6C（lo）巨噬细胞的时间过渡期间发现的转录变化相似。在体内，消退素D2增加Ly6C（lo）巨噬细胞和再生肌肉的功能改善。这些结果揭示了先天免疫细胞的动态脂质介质特征，并为它们在肌肉再生中的可利用效应器作用提供了概念证明。
Muscle damage elicits a sterile immune response that facilitates complete regeneration. Here, we used mass spectrometry-based lipidomics to map the mediator lipidome during the transition from inflammation to resolution and regeneration in skeletal muscle injury. We observed temporal regulation of glycerophospholipids and production of pro-inflammatory lipid mediators (for example, leukotrienes and prostaglandins) and specialized pro-resolving lipid mediators (for example, resolvins and lipoxins) that were modulated by ibuprofen. These time-dependent profiles were recapitulated in sorted neutrophils and Ly6C(hi) and Ly6C(lo) muscle-infiltrating macrophages, with a distinct pro-resolving signature observed in Ly6C(lo) macrophages. RNA sequencing of macrophages stimulated with resolvin D2 showed similarities to transcriptional changes found during the temporal transition from Ly6C(hi) macrophage to Ly6C(lo) macrophage. In vivo, resolvin D2 increased Ly6C(lo) macrophages and functional improvement of the regenerating muscle. These results reveal dynamic lipid mediator signatures of innate immune cells and provide a proof of concept for their exploitable effector roles in muscle regeneration.