Deep skin fibroblast-mediated macrophage recruitment supports acute wound healing

Authors

• Veronica M. Amuso, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA.
• MaryEllen R. Haas, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA.
• Paula O. Cooper, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA.
• Ranojoy Chatterjee, Computational Biology Institute, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC 20052, USA.
• Sana Hafiz, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA.
• Shatha Salameh, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA.
• Chiraag Gohel, Computational Biology Institute, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC 20052, USA.
• Miguel F. Mazumder, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA.
• Violet Josephson, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA.
• Khatereh Khorsandi, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA.
• Anelia Horvath, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA.
• Ali Rahnavard, Computational Biology Institute, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC 20052, USA.
• Brett A. Shook, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA.

Document Type

Journal Article

Publication Date

8-10-2024

Journal

bioRxiv : the preprint server for biology

DOI

10.1101/2024.08.09.607357

Keywords

CCL2; fibroblast; macrophage; single nuclei RNA-sequencing; wound healing

Abstract

Epithelial and immune cells have long been appreciated for their contribution to the early immune response after injury; however, much less is known about the role of mesenchymal cells. Using single nuclei RNA-sequencing, we defined changes in gene expression associated with inflammation at 1-day post-wounding (dpw) in mouse skin. Compared to keratinocytes and myeloid cells, we detected enriched expression of pro-inflammatory genes in fibroblasts associated with deeper layers of the skin. In particular, SCA1+ fibroblasts were enriched for numerous chemokines, including CCL2, CCL7, and IL33 compared to SCA1- fibroblasts. Genetic deletion of Ccl2 in fibroblasts resulted in fewer wound bed macrophages and monocytes during injury-induced inflammation with reduced revascularization and re-epithelialization during the proliferation phase of healing. These findings highlight the important contribution of deep skin fibroblast-derived factors to injury-induced inflammation and the impact of immune cell dysregulation on subsequent tissue repair.

APA Citation

Amuso, Veronica M.; Haas, MaryEllen R.; Cooper, Paula O.; Chatterjee, Ranojoy; Hafiz, Sana; Salameh, Shatha; Gohel, Chiraag; Mazumder, Miguel F.; Josephson, Violet; Khorsandi, Khatereh; Horvath, Anelia; Rahnavard, Ali; and Shook, Brett A., "Deep skin fibroblast-mediated macrophage recruitment supports acute wound healing" (2024). GW Authored Works. Paper 5489.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5489

Department

Biochemistry and Molecular Medicine