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Tissue iron promotes wound repair via M2 macrophage polarisation and the chemokines CCL17 and CCL22

Wilkinson, Holly N.; Roberts, Elizabeth Rose; Stafford, Amber Rose; Banyard, Kayleigh L.; Matteucci, Paolo; Mace, Kimberly Ann; Hardman, Matthew J.

Authors

Elizabeth Rose Roberts

Amber Rose Stafford

Kayleigh L. Banyard

Paolo Matteucci

Kimberly Ann Mace



Abstract

Macrophages are important for effective iron recycling and erythropoiesis, but they also play a crucial role in wound healing, orchestrating tissue repair. Recently, we demonstrated a significant accumulation of iron in healing wounds and a requirement of iron for effective repair. Herein, we sought to determine the influence of iron on macrophage function in the context of wound healing. Interestingly, wound macrophages extensively sequestered iron throughout healing, associated with a prohealing M2 phenotype. In delayed healing diabetic mouse wounds, both macrophage polarization and iron sequestration were impaired. In vitro studies revealed that iron promotes differentiation, while skewing macrophages toward a hypersecretory M2-like polarization state. These macrophages produced high levels of chemokine (C-C motif) ligands 17 and 22, promoting wound reepithelialization and extracellular matrix deposition in a human ex vivo wound healing model. Together, these findings reveal a novel, unappreciated role for iron in modulating macrophage behavior to promote subsequent wound repair. These findings support therapeutic evaluation of iron use to promote wound healing in the clinic.

Citation

Roberts, E. R., Stafford, A. R., Mace, K. A., Wilkinson, H. N., Roberts, E. R., Stafford, A. R., …Hardman, M. J. (2019). Tissue iron promotes wound repair via M2 macrophage polarisation and the chemokines CCL17 and CCL22. American Journal of Pathology, 189(11), 2196-2208. https://doi.org/10.1016/j.ajpath.2019.07.015

Journal Article Type Article
Acceptance Date Jul 25, 2019
Online Publication Date Aug 27, 2019
Publication Date Nov 1, 2019
Deposit Date Oct 15, 2019
Publicly Available Date Oct 16, 2019
Journal American Journal of Pathology
Print ISSN 0002-9440
Electronic ISSN 1525-2191
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 189
Issue 11
Pages 2196-2208
DOI https://doi.org/10.1016/j.ajpath.2019.07.015
Keywords Pathology and Forensic Medicine
Public URL https://hull-repository.worktribe.com/output/2689065
Publisher URL https://www.sciencedirect.com/science/article/pii/S0002944019306716?via%3Dihub

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Copyright Statement
Copyright 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved





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