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Macrophages are necessary for epimorphic regeneration in African spiny mice

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...

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Detalles Bibliográficos
Autores principales: Simkin, Jennifer, Gawriluk, Thomas R, Gensel, John C, Seifert, Ashley W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433844/
https://www.ncbi.nlm.nih.gov/pubmed/28508748
http://dx.doi.org/10.7554/eLife.24623
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author Simkin, Jennifer
Gawriluk, Thomas R
Gensel, John C
Seifert, Ashley W
author_facet Simkin, Jennifer
Gawriluk, Thomas R
Gensel, John C
Seifert, Ashley W
author_sort Simkin, Jennifer
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.24623.001
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spelling pubmed-54338442017-05-17 Macrophages are necessary for epimorphic regeneration in African spiny mice Simkin, Jennifer Gawriluk, Thomas R Gensel, John C Seifert, Ashley W eLife Cell Biology 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. DOI: http://dx.doi.org/10.7554/eLife.24623.001 eLife Sciences Publications, Ltd 2017-05-16 /pmc/articles/PMC5433844/ /pubmed/28508748 http://dx.doi.org/10.7554/eLife.24623 Text en © 2017, Simkin et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Simkin, Jennifer
Gawriluk, Thomas R
Gensel, John C
Seifert, Ashley W
Macrophages are necessary for epimorphic regeneration in African spiny mice
title Macrophages are necessary for epimorphic regeneration in African spiny mice
title_full Macrophages are necessary for epimorphic regeneration in African spiny mice
title_fullStr Macrophages are necessary for epimorphic regeneration in African spiny mice
title_full_unstemmed Macrophages are necessary for epimorphic regeneration in African spiny mice
title_short Macrophages are necessary for epimorphic regeneration in African spiny mice
title_sort macrophages are necessary for epimorphic regeneration in african spiny mice
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433844/
https://www.ncbi.nlm.nih.gov/pubmed/28508748
http://dx.doi.org/10.7554/eLife.24623
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AT seifertashleyw macrophagesarenecessaryforepimorphicregenerationinafricanspinymice