Efferocytosis in the pathogenesis and therapeutic significance of lung diseases

Abstract:

Efferocytosis, the highly coordinated process by which phagocytes clear apoptotic cells, is essential for maintaining pulmonary homeostasis and regulating immune responses under both physiological and pathological conditions. This process relies on the precise integration of “find-me,” “eat-me,” and “don’t eat-me” signals that enable phagocytes, including macrophages and dendritic cells, to identify and engulf apoptotic cells, thereby preventing secondary necrosis and excessive inflammation. Efferocytosis not only removes harmful cellular debris but also promotes the release of anti-inflammatory cytokines and drives immunometabolic reprogramming, collectively facilitating inflammation resolution and tissue repair. Impaired efferocytosis leads to the accumulation of apoptotic cells and the release of damage-associated molecular patterns, contributing to the pathogenesis of multiple lung diseases, including chronic obstructive pulmonary disease, asthma, acute respiratory distress syndrome, and idiopathic pulmonary fibrosis. In this review, we summarize the process and the mechanisms of efferocytosis, discuss the roles of efferocytosis in the pathogenesis of lung diseases, and highlight recent advances in efferocytosis-centered therapies, providing new strategies for treating lung diseases by modulating efferocytosis.