Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury
Abstract Successful tissue repair requires the activities of myeloid cells such as monocytes and macrophages that guide the progression of inflammation and healing outcome. Immunoregenerative materials leverage the function of endogenous immune cells to orchestrate complex mechanisms of repair; howe...
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Nature Portfolio
2017
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oai:doaj.org-article:97d46e2fdbb240baa119d3313447e5722021-12-02T12:32:45ZNon-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury10.1038/s41598-017-00477-12045-2322https://doaj.org/article/97d46e2fdbb240baa119d3313447e5722017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00477-1https://doaj.org/toc/2045-2322Abstract Successful tissue repair requires the activities of myeloid cells such as monocytes and macrophages that guide the progression of inflammation and healing outcome. Immunoregenerative materials leverage the function of endogenous immune cells to orchestrate complex mechanisms of repair; however, a deeper understanding of innate immune cell function in inflamed tissues and their subsequent interactions with implanted materials is necessary to guide the design of these materials. Blood monocytes exist in two primary subpopulations, characterized as classical inflammatory or non-classical. While classical monocytes extravasate into inflamed tissue and give rise to macrophages or dendritic cells, the recruitment kinetics and functional role of non-classical monocytes remains unclear. Here, we demonstrate that circulating non-classical monocytes are directly recruited to polymer films within skin injuries, where they home to a perivascular niche and generate alternatively activated, wound healing macrophages. Selective labeling of blood monocyte subsets indicates that non-classical monocytes are biased progenitors of alternatively activated macrophages. On-site delivery of the immunomodulatory small molecule FTY720 recruits S1PR3-expressing non-classical monocytes that support vascular remodeling after injury. These results elucidate a previously unknown role for blood-derived non-classical monocytes as contributors to alternatively activated macrophages, highlighting them as key regulators of inflammatory response and regenerative outcome.Claire E. OlingyCheryl L. San EmeterioMolly E. OgleJack R. KriegerAnthony C. BruceDavid D. PfauBrett T. JordanShayn M. PeirceEdward A. BotchweyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017) |
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Medicine R Science Q Claire E. Olingy Cheryl L. San Emeterio Molly E. Ogle Jack R. Krieger Anthony C. Bruce David D. Pfau Brett T. Jordan Shayn M. Peirce Edward A. Botchwey Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury |
description |
Abstract Successful tissue repair requires the activities of myeloid cells such as monocytes and macrophages that guide the progression of inflammation and healing outcome. Immunoregenerative materials leverage the function of endogenous immune cells to orchestrate complex mechanisms of repair; however, a deeper understanding of innate immune cell function in inflamed tissues and their subsequent interactions with implanted materials is necessary to guide the design of these materials. Blood monocytes exist in two primary subpopulations, characterized as classical inflammatory or non-classical. While classical monocytes extravasate into inflamed tissue and give rise to macrophages or dendritic cells, the recruitment kinetics and functional role of non-classical monocytes remains unclear. Here, we demonstrate that circulating non-classical monocytes are directly recruited to polymer films within skin injuries, where they home to a perivascular niche and generate alternatively activated, wound healing macrophages. Selective labeling of blood monocyte subsets indicates that non-classical monocytes are biased progenitors of alternatively activated macrophages. On-site delivery of the immunomodulatory small molecule FTY720 recruits S1PR3-expressing non-classical monocytes that support vascular remodeling after injury. These results elucidate a previously unknown role for blood-derived non-classical monocytes as contributors to alternatively activated macrophages, highlighting them as key regulators of inflammatory response and regenerative outcome. |
format |
article |
author |
Claire E. Olingy Cheryl L. San Emeterio Molly E. Ogle Jack R. Krieger Anthony C. Bruce David D. Pfau Brett T. Jordan Shayn M. Peirce Edward A. Botchwey |
author_facet |
Claire E. Olingy Cheryl L. San Emeterio Molly E. Ogle Jack R. Krieger Anthony C. Bruce David D. Pfau Brett T. Jordan Shayn M. Peirce Edward A. Botchwey |
author_sort |
Claire E. Olingy |
title |
Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury |
title_short |
Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury |
title_full |
Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury |
title_fullStr |
Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury |
title_full_unstemmed |
Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury |
title_sort |
non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/97d46e2fdbb240baa119d3313447e572 |
work_keys_str_mv |
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1718393993524412416 |