ZBTB46 regulates angiogenesis and macrophage phenotypes during the wound-healing process 9259

Abstract Description Skin injuries are among the costliest problems worldwide. A better understanding of the regulatory mechanisms involved in repair could lead to discovering novel regulators that enhance the healing process. During wound healing, precise and well-timed angiogenesis promotion is vital for optimal tissue repair. We have shown that ZBTB46, a transcription factor and marker of classical dendritic cells, negatively controls angiogenesis and promotes immunosuppressive myeloid lineage output over the dendritic cell program in tumors. Here, we employed the excisional wound model to investigate whether Zbtb46 KO mice exhibit better repair by promoting angiogenesis and modulating immunity. Zbtb46 KO mice exhibited enhanced wound healing, while the endothelial or hematopoietic-specific Zbtb46 KO did not significantly improve wound healing. These results suggest that Zbtb46 downregulation in endothelial and hematopoietic cells is needed for optimal wound healing. To discover how Zbtb46 deletion affects angiogenesis and immunity during wound healing, we conducted wound skin analysis using flow cytometry. We observed an increased CD31+ cells and macrophages, particularly M2-type macrophages, in the skin on day 3 after the injury. We found increased vessel formation in the injured skin on day 3 post-injury. These findings suggest that targeting the regulation of ZBTB46 could be a novel therapeutic strategy for treating wounds by modulating angiogenesis and immunity to enhance tissue repair. Funding Sources CRM DPS Program Travel Award Topic Categories Translational and Interventional Immunology (TI)