Resolution mediator chemerin15 reprograms the wound microenvironment to promote repair and reduce scarring

Jenna L Cash, Mark D Bass, Jessica Campbell, Matthew Barnes, Paul Kubes, Paul B Martin

Research output: Contribution to journalArticle (Academic Journal)

35 Citations (Scopus)

Abstract

Disorders of cutaneous repair can cause disability or death given that skin functions as a protective barrier against the external environment. The inflammatory response triggered by tissue damage is thought to play both positive (e.g., pathogen-killing) and negative (e.g., scarring) roles in repair [1-3]. Inflammatory resolution mediators such as chemerin15 (C15) control the magnitude and duration of the inflammatory response; however, their role in wound repair and scarring is unknown [4-8]. Here, we show that the C15 precursor, chemerin, and its receptor, ChemR23, are both upregulated after skin damage and that the receptor is expressed by macrophages, neutrophils, and keratinocytes. Dynamic live-imaging studies of murine cutaneous wounds demonstrate that C15 delivery dampens the immediate intravascular inflammatory events, including platelet adhesion to neutrophils, an important event in driving leukocyte recruitment. C15 administration indirectly accelerates wound closure while altering fibroblast-mediated collagen deposition and alignment to reduce scarring. Macrophage recruitment is restricted to the immediate wound site rather than spilling extensively into the adjacent tissue as in control wounds, and macrophage phenotype in C15-treated wounds is skewed toward a less inflammatory phenotype with reduced iNOS, increased Arginase-1, and lower wound tumor necrosis factor α (TNF-α) expression. Modulation of inflammatory resolution pathways in acute and chronic wounds may therefore provide a novel therapeutic avenue to improve repair and reduce scarring.

Original languageEnglish
Pages (from-to)1406-14
Number of pages9
JournalCurrent Biology
Volume24
Issue number12
DOIs
Publication statusPublished - 16 Jun 2014

Bibliographical note

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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