Defective efferocytosis in diabetes: molecular mechanisms and emerging therapeutic strategies

Diabetes is associated with oxidative stress, systemic immune dysregulation and chronic low-grade inflammation, which contributes to a wide spectrum of microvascular and macrovascular complications. Efferocytosis, the phagocytic clearance of apoptotic cells by macrophages and dendritic cells, is essential for inflammation resolution and tissue repair. Defective efferocytosis has been increasingly implicated in the progression of diabetes and several of its major complications, including atherosclerosis, nephropathy, retinopathy, impaired wound healing, and osteoporosis.

This narrative review is prepared through a focused literature search of studies investigating efferocytosis in diabetes, elucidates how its disruption contributes to the progression of diabetic complications, and further highlight emerging therapeutic strategies aimed at regulating efferocytosis. This paper is expected to provide direction and outlook for the research on efferocytosis and diabetes.

Efferocytosis regulation involves a coordinated cascade of find-me signals, engulfment receptors, intracellular cytoskeletal remodeling, and metabolic reprogramming. This review summarizes the key molecular changes of defective efferocytosis and pathological changes in diabetic complications. Importantly, emerging preclinical studies have demonstrated that restoring efferocytosis ameliorate inflammation, promote tissue regeneration, and interrupt the progression of diabetic complications.

Efferocytosis not only illuminates fundamental aspects of immune regulation but also opens up new therapeutic possibilities. As the field continues to evolve, integrating efferocytosis-based interventions into the broader therapeutic landscape of diabetes may represent a paradigm shift in the management of its chronic complications.