Macrophages are necessary for epimorphic regeneration in African spiny mice

Jennifer Simkin; Thomas R. Gawriluk; John C. Gensel; Ashley W. Seifert

doi:10.7554/eLife.24623

Macrophages are necessary for epimorphic regeneration in African spiny mice

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144 Scopus citations

Abstract

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.

Original language	English
Article number	e24623
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.24623
State	Published - May 16 2017

Bibliographical note

Publisher Copyright:
© Simkin et al.

Funding

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.

Funders	Funder number
Office of the Vice President for Research
National Science Foundation Arctic Social Science Program
National Childhood Cancer Registry – National Cancer Institute	P30 CA177558
Office of International Science and Engineering	IOS-1353713
University of Kentucky
University of Kentucky Markey Comprehensive Cancer Center

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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10.7554/eLife.24623

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abstract = "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.",

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Macrophages are necessary for epimorphic regeneration in African spiny mice

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

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