Macrophages are necessary for epimorphic regeneration in African spiny mice
Macrophages are necessary for epimorphic regeneration in African spiny mice
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DOI：
10.7554/elife.24623
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发表时间：
2017-05-16
期刊：
影响因子：
7.7
通讯作者：
Seifert, Ashley W.
中科院分区：
文献类型：
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作者：
Simkin, Jennifer;Gawriluk, Thomas R.;Seifert, Ashley W.
免疫系统如何影响组织再生尚不清楚。在这项研究中，我们使用了一种新兴的表态再生哺乳动物模型——非洲刺鼠，来检查基于细胞的炎症，并测试了巨噬细胞对于再生是必需的假设。通过直接比较再生过程中 4 毫米耳损伤（Acomys cahirinus）和疤痕形成（Mus musculus）中的炎症细胞活化，我们发现这两个物种都表现出急性炎症反应，疤痕形成的特点是髓过氧化物酶活性更强。相比之下，再生过程中 ROS 的产生更强、更持久。通过在损伤期间耗尽巨噬细胞，我们证明了这些细胞刺激再生的功能要求。重要的是，活化的巨噬细胞亚型的空间分布在再生过程中是独特的，促炎巨噬细胞无法浸润再生胚基。总之，我们的结果证明了炎症细胞在调节再生反应中的重要作用。
How the immune system affects tissue regeneration is not well understood. In this study, we used an emerging mammalian model of epimorphic regeneration, the African spiny mouse, to examine cell-based inflammation and tested the hypothesis that macrophages are necessary for regeneration. By directly comparing inflammatory cell activation in a 4 mm ear injury during regeneration (Acomys cahirinus) and scarring (Mus musculus), we found that both species exhibited an acute inflammatory response, with scarring characterized by stronger myeloperoxidase activity. In contrast, ROS production was stronger and more persistent during regeneration. By depleting macrophages during injury, we demonstrate a functional requirement for these cells to stimulate regeneration. Importantly, the spatial distribution of activated macrophage subtypes was unique during regeneration with pro-inflammatory macrophages failing to infiltrate the regeneration blastema. Together, our results demonstrate an essential role for inflammatory cells to regulate a regenerative response.