Simkin Jennifer, Gawriluk Thomas R, Gensel John C, Seifert Ashley W
Department of Biology, University of Kentucky, Lexington, United States.
Department of Physiology, University of Kentucky, Lexington, United States.
Elife. 2017 May 16;6:e24623. doi: 10.7554/eLife.24623.
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 () and scarring (), 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.
免疫系统如何影响组织再生尚未得到充分理解。在本研究中，我们使用了一种新兴的形态再生哺乳动物模型——非洲刺毛鼠，来研究基于细胞的炎症，并测试巨噬细胞对再生是否必要这一假设。通过直接比较再生（）和瘢痕形成（）过程中4毫米耳部损伤时的炎性细胞激活情况，我们发现两个物种均表现出急性炎症反应，瘢痕形成的特征是髓过氧化物酶活性更强。相比之下，再生过程中活性氧的产生更强且更持久。通过在损伤期间清除巨噬细胞，我们证明了这些细胞对刺激再生的功能需求。重要的是，再生过程中活化巨噬细胞亚型的空间分布是独特的，促炎巨噬细胞无法浸润再生芽基。总之，我们的结果证明了炎性细胞在调节再生反应中起着至关重要的作用。
