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

• Type of Material: Article
• Authors: Claire E. Olingy, Georgia Institute of Technology; Cheryl L. San Emeterio, Georgia Institute of Technology; Molly E. Ogle, Georgia Institute of Technology; Jack R. Krieger, Georgia Institute of Technology; Anthony C. Bruce, University of Virginia; David D. Pfau, Georgia Institute of Technology; Brett T. Jordan, Georgia Institute of Technology; Shayne M. Peirce, Georgia Institute of Technology; Edward Botchwey, Emory University
• Language: English
• Date: 2017-12-01
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © 2017 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-017-00477-1
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 7
• Issue: 1
• Start Page: 447
• End Page: 447
• Grant/Funding Information: This work was supported by the National Institutes of Health grants R01AR056445-01A2 and R01DE019935-01, National Science Foundation Graduate Research Fellowship under Grant No. DGE-1148903, American Heart Association Grant 15PRE25090024, P.E.O. Scholar Award to Claire Olingy, The Hartwell Foundation, and Georgia Institute of Technology President’s Undergraduate Research Award to David Pfau.
• Research Categories: Engineering, Biomedical

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.