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; 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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Olingy CE,San Emeterio CL,Ogle ME,Krieger JR,Bruce AC,Pfau DD,Jordan BT,Peirce SM,Botchwey EA

doi

10.1038/s41598-017-00477-1

subject

Has Abstract

pub_date

2017-03-27 00:00:00

pages

447

issue

1

issn

2045-2322

pii

10.1038/s41598-017-00477-1

journal_volume

7

pub_type

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