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Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury

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 de...

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Autores principales: Olingy, Claire E., San Emeterio, Cheryl L., Ogle, Molly E., Krieger, Jack R., Bruce, Anthony C., Pfau, David D., Jordan, Brett T., Peirce, Shayn M., Botchwey, Edward A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428475/
https://www.ncbi.nlm.nih.gov/pubmed/28348370
http://dx.doi.org/10.1038/s41598-017-00477-1
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author Olingy, Claire E.
San Emeterio, Cheryl L.
Ogle, Molly E.
Krieger, Jack R.
Bruce, Anthony C.
Pfau, David D.
Jordan, Brett T.
Peirce, Shayn M.
Botchwey, Edward A.
author_facet Olingy, Claire E.
San Emeterio, Cheryl L.
Ogle, Molly E.
Krieger, Jack R.
Bruce, Anthony C.
Pfau, David D.
Jordan, Brett T.
Peirce, Shayn M.
Botchwey, Edward A.
author_sort Olingy, Claire E.
collection PubMed
description 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.
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spelling pubmed-54284752017-05-15 Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury Olingy, Claire E. San Emeterio, Cheryl L. Ogle, Molly E. Krieger, Jack R. Bruce, Anthony C. Pfau, David D. Jordan, Brett T. Peirce, Shayn M. Botchwey, Edward A. Sci Rep Article 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. Nature Publishing Group UK 2017-03-27 /pmc/articles/PMC5428475/ /pubmed/28348370 http://dx.doi.org/10.1038/s41598-017-00477-1 Text en © The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Olingy, Claire E.
San Emeterio, Cheryl L.
Ogle, Molly E.
Krieger, Jack R.
Bruce, Anthony C.
Pfau, David D.
Jordan, Brett T.
Peirce, Shayn M.
Botchwey, Edward A.
Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428475/
https://www.ncbi.nlm.nih.gov/pubmed/28348370
http://dx.doi.org/10.1038/s41598-017-00477-1
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