Non-healing wounds in Type 2 Diabetes (T2D) patients represent the most common cause of amputation in the US, with an associated 5-year mortality of nearly 50%. Our lab has examined tissue from both T2D murine models and human wounds in order to explore mechanisms contributing to impaired wound healing. Current published data in the field point to macrophage function serving a pivotal role in orchestrating appropriate wound healing. Wound macrophages in mice and patients with T2D are characterized by a persistent inflammatory state; however, the mechanisms that control this persistent inflammatory state are unknown. Current literature demonstrates that gene regulation through histone modifications, DNA modifications, and microRNA can influence macrophage plasticity during wound healing. Further, accumulating studies reveal the importance of cells such as adipocytes, infiltrating immune cells (PMNs and T cells), and keratinocytes secrete factors that may help drive macrophage polarization. This review will examine the role of macrophages in the wound healing process, along with their function and interactions with other cells, and how it is perturbed in T2D. We also explore epigenetic factors that regulate macrophage polarization in wounds, while highlighting the emerging role of other cell types that may influence macrophage phenotype following tissue injury.

2 型糖尿病 (T2D) 患者的未愈合伤口是美国最常见的截肢原因，相关的 5 年死亡率接近 50%。我们的实验室检查了 T2D 小鼠模型和人类伤口的组织，以探索导致伤口愈合受损的机制。该领域当前公布的数据表明巨噬细胞功能在协调适当的伤口愈合中起着关键作用。小鼠和 T2D 患者的伤口巨噬细胞以持续炎症状态为特征；然而，控制这种持续炎症状态的机制尚不清楚。目前的文献表明，通过组蛋白修饰、DNA 修饰和 microRNA 进行的基因调控可以影响伤口愈合过程中的巨噬细胞可塑性。更远，越来越多的研究揭示了脂肪细胞、浸润性免疫细胞（PMN 和 T 细胞）和角质形成细胞等细胞的重要性，这些细胞分泌可能有助于驱动巨噬细胞极化的因子。这篇综述将研究巨噬细胞在伤口愈合过程中的作用，以及它们的功能和与其他细胞的相互作用，以及它如何在 T2D 中受到干扰。我们还探讨了调节伤口巨噬细胞极化的表观遗传因素，同时强调了可能影响组织损伤后巨噬细胞表型的其他细胞类型的新兴作用。以及它如何在 T2D 中受到干扰。我们还探讨了调节伤口巨噬细胞极化的表观遗传因素，同时强调了可能影响组织损伤后巨噬细胞表型的其他细胞类型的新兴作用。以及它如何在 T2D 中受到干扰。我们还探讨了调节伤口巨噬细胞极化的表观遗传因素，同时强调了可能影响组织损伤后巨噬细胞表型的其他细胞类型的新兴作用。