Honda Azusa, Koike Hiroyuki, Dohi Teruyuki, Toyohara Eri, Hayakawa Sumio, Tobe Kazuyuki, Manabe Ichiro, Ogawa Rei, Oishi Yumiko
Department of Biochemistry & Molecular Biology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
EMBO Rep. 2025 Jun 10. doi: 10.1038/s44319-025-00496-4.
Wound healing is a multifaceted and dynamic sequence of tissue repair and regeneration processes involving interrelated stages: inflammation, regeneration, and remodeling. Throughout these processes, macrophages change their phenotypes and interact with cells and extracellular components to facilitate healing. In particular, macrophages expressing the surface marker CD206 associate with inflammation resolution and tissue repair. However, how CD206 macrophages contribute to these processes is insufficiently understood. Here, using a mouse model of CD206 macrophage depletion and single-cell transcriptomics, we report that selective depletion of CD206 macrophages results in modest but significant delays in wound healing, prolongs inflammation, and significantly reduces the number of Gpnmb fibroblasts in injured skin. Single-cell data suggest that CD206 macrophages communicate with Gpnmb fibroblasts via multiple pathways. Notably, topical administration of PDGF-AA to wounds of CD206 macrophage-depleted mice restores healing processes, identifying PDGF-A signaling from CD206 macrophages to PDGFRA on fibroblasts as an important mechanism promoting wound healing. Collectively, these data demonstrate that CD206 macrophages communicate with Gpnmb fibroblasts to activate their proliferation and extracellular matrix deposition in wound healing.
伤口愈合是一个多方面的动态组织修复和再生过程序列，涉及相互关联的阶段：炎症、再生和重塑。在这些过程中，巨噬细胞会改变其表型，并与细胞和细胞外成分相互作用以促进愈合。特别是，表达表面标志物CD206的巨噬细胞与炎症消退和组织修复相关。然而，CD206巨噬细胞如何促成这些过程还了解不足。在此，我们使用CD206巨噬细胞耗竭的小鼠模型和单细胞转录组学，报告CD206巨噬细胞的选择性耗竭导致伤口愈合出现适度但显著的延迟，延长炎症反应，并显著减少受伤皮肤中Gpnmb成纤维细胞的数量。单细胞数据表明CD206巨噬细胞通过多种途径与Gpnmb成纤维细胞进行通信。值得注意的是，向CD206巨噬细胞耗竭小鼠的伤口局部施用血小板衍生生长因子AA（PDGF-AA）可恢复愈合过程，确定从CD206巨噬细胞到成纤维细胞上的血小板衍生生长因子受体A（PDGFRA）的PDGF-A信号传导是促进伤口愈合的重要机制。总的来说，这些数据表明CD206巨噬细胞与Gpnmb成纤维细胞通信，以激活它们在伤口愈合中的增殖和细胞外基质沉积。
