The study investigates the role of macrophages in regulating healing-associated fibroblasts in diabetic wounds. Using bioinformatic tools, the researchers identified genes significantly altered in diabetic skin, focusing on proinflammation and angiogenesis pathways. In a mouse model of diabetic wound healing, they found that macrophages from diabetic wounds had compromised expression of key factors involved in wound healing, such as IL1β, IL6, IL10, VEGF-A, MMP1, MMP3, MMP11, CHI3L1, and VEGF-A. Co-culture experiments showed that M1 macrophages from non-diabetic wounds could enhance the expression of these factors in fibroblasts from diabetic wounds, while M1 macrophages from diabetic wounds reduced their expression. Additionally, co-culture with non-diabetic macrophages or macrophages treated with IL6 (a pro-inflammatory cytokine) increased the expression of these factors in fibroblasts from diabetic wounds. The study also demonstrated that macrophage-specific expression of IL6 improved wound healing and angiogenesis in diabetic mice. These findings suggest that M1/proinflammatory macrophages play a crucial role in activating healing-associated fibroblasts, and that IL6 treatment could be a promising therapeutic strategy to correct this defect in diabetic wounds.The study investigates the role of macrophages in regulating healing-associated fibroblasts in diabetic wounds. Using bioinformatic tools, the researchers identified genes significantly altered in diabetic skin, focusing on proinflammation and angiogenesis pathways. In a mouse model of diabetic wound healing, they found that macrophages from diabetic wounds had compromised expression of key factors involved in wound healing, such as IL1β, IL6, IL10, VEGF-A, MMP1, MMP3, MMP11, CHI3L1, and VEGF-A. Co-culture experiments showed that M1 macrophages from non-diabetic wounds could enhance the expression of these factors in fibroblasts from diabetic wounds, while M1 macrophages from diabetic wounds reduced their expression. Additionally, co-culture with non-diabetic macrophages or macrophages treated with IL6 (a pro-inflammatory cytokine) increased the expression of these factors in fibroblasts from diabetic wounds. The study also demonstrated that macrophage-specific expression of IL6 improved wound healing and angiogenesis in diabetic mice. These findings suggest that M1/proinflammatory macrophages play a crucial role in activating healing-associated fibroblasts, and that IL6 treatment could be a promising therapeutic strategy to correct this defect in diabetic wounds.