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.

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

Wilkinson, H. N., Roberts, E. R., Stafford, A. R., Banyard, K. L., Matteucci, P., Mace, K. A., & 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
• 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
• Contract Date: Oct 15, 2019