The Crosstalk Between Efferocytosis and Macrophage Polarization in Diabetic Wounds: A Comprehensive Review

Yuxin He,1,2 Jie Hu,1,2 Anqi Ma,1,2 Peiyang Du,1,2 Mengdie Yang,1,2 Xia Xiong,2 Yongqiong Deng1 1Department of Dermatology, Chengdu Integrated TCM and Western Medicine Hospital, Chengdu, Sichuan, 610041, People’s Republic of China; 2Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of ChinaCorrespondence: Xia Xiong, Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Email [email protected] Yongqiong Deng, Department of Dermatology, Chengdu Integrated TCM and Western Medicine Hospital, Chengdu, Sichuan, 610041, People’s Republic of China, Email [email protected]: Chronic refractory cutaneous wounds are major complications of diabetes. A hallmark of this pathology is persistent inflammation, driven in part by the accumulation of apoptotic cells (ACs) due to impaired clearance. Efferocytosis, as the primary process for removing ACs, was disordered when triggered by the diabetic microenvironment, further leading to impaired macrophage polarization and consequently delaying wound healing. This review also focuses on the abnormal crosstalk between efferocytosis and macrophage polarization and its modulated signaling pathways governing this axis, and reviewing potential novel therapeutic strategies targeting the restoration of clearing ACs. This review may offer new insights and directions for overcoming current treatment drawbacks in diabetic wound healing.Keywords: apoptotic cells, efferocytosis, macrophage polarization, diabetic wound healing