Deep skin fibroblast-mediated macrophage recruitment supports acute wound healing

Amuso, V.; Haas, M.; Cooper, P.; Chatterjee, R.; Hafiz, S.; Salameh, S.; Gohel, C.; Mazumder, M.; Josephson, V.; Khorsandi, K.; Horvath, A.; Rahnavard, A.; Shook, B.

doi:10.1101/2024.08.09.607357

bioRxiv · 10.1101/2024.08.09.607357

Deep skin fibroblast-mediated macrophage recruitment supports acute wound healing

Amuso, V.·Haas, M.·Cooper, P.·Chatterjee, R.·Hafiz, S.·Salameh, S.·Gohel, C.·Mazumder, M.·Josephson, V.·Khorsandi, K.·Horvath, A.·Rahnavard, A.·Shook, B.

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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.

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Amuso, V., Haas, M., Cooper, P., Chatterjee, R., Hafiz, S., Salameh, S., Gohel, C., Mazumder, M., Josephson, V., Khorsandi, K., Horvath, A., Rahnavard, A., Shook, B.. 2024-08-10. Deep skin fibroblast-mediated macrophage recruitment supports acute wound healing. https://doi.org/10.1101/2024.08.09.607357

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