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.
|State||Published - May 16 2017|
Bibliographical noteFunding Information:
The authors would like to thank Jennifer Strange and Greg Bauman of the University of Kentucky Flow Cytometry and Cell Sorting Core Facility, which is supported in part by the Office of the Vice President for Research, the Markey Cancer Center and an NCI Center Core Support Grant (P30 CA177558) to the University of Kentucky Markey Cancer Center. We thank Jeremiah Smith, Shishir Biswas, and Chanung Wang for help with A. cahirinus transcriptomic and genomic data, and members of the Seifert and Gensel labs for insightful discussion. This work was supported by a grant from the National Science Foundation (NSF) and the Office for International Science and Engineering (OISE) (IOS-1353713) to AWS. JS is supported by a University of Kentucky Postdoctoral Research Fellowship.
© Simkin et al.
ASJC Scopus subject areas
- Neuroscience (all)
- Immunology and Microbiology (all)
- Biochemistry, Genetics and Molecular Biology (all)