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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Main Authors: Jennifer Simkin, Thomas R Gawriluk, John C Gensel, Ashley W Seifert
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-05-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/24623
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author Jennifer Simkin
Thomas R Gawriluk
John C Gensel
Ashley W Seifert
author_facet Jennifer Simkin
Thomas R Gawriluk
John C Gensel
Ashley W Seifert
author_sort Jennifer Simkin
collection DOAJ
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.
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spelling doaj.art-bbd57cb6248d4347bc890fabd4d41f092022-12-22T03:33:22ZengeLife Sciences Publications LtdeLife2050-084X2017-05-01610.7554/eLife.24623Macrophages are necessary for epimorphic regeneration in African spiny miceJennifer Simkin0https://orcid.org/0000-0002-6122-4222Thomas R Gawriluk1https://orcid.org/0000-0001-9868-9704John C Gensel2https://orcid.org/0000-0001-8980-108XAshley W Seifert3https://orcid.org/0000-0001-6576-3664Department of Biology, University of Kentucky, Lexington, United States; Department of Physiology, University of Kentucky, Lexington, United States; Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, United StatesDepartment of Biology, University of Kentucky, Lexington, United StatesDepartment of Physiology, University of Kentucky, Lexington, United States; Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, United StatesDepartment of Biology, University of Kentucky, Lexington, United StatesHow 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.https://elifesciences.org/articles/24623Acomysepimorphic regenerationmacrophagesinflammation
spellingShingle Jennifer Simkin
Thomas R Gawriluk
John C Gensel
Ashley W Seifert
Macrophages are necessary for epimorphic regeneration in African spiny mice
eLife
Acomys
epimorphic regeneration
macrophages
inflammation
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 Acomys
epimorphic regeneration
macrophages
inflammation
url https://elifesciences.org/articles/24623
work_keys_str_mv AT jennifersimkin macrophagesarenecessaryforepimorphicregenerationinafricanspinymice
AT thomasrgawriluk macrophagesarenecessaryforepimorphicregenerationinafricanspinymice
AT johncgensel macrophagesarenecessaryforepimorphicregenerationinafricanspinymice
AT ashleywseifert macrophagesarenecessaryforepimorphicregenerationinafricanspinymice