Research Progress on Efferocytosis Dysfunction in Rheumatoid Arthritis

Macrophages serve as the core immune effector cells within the RA synovium, and their functional abnormalities are pivotal in sustaining inflammation and tissue damage. Efferocytosis refers to the highly efficient, immunosuppressive clearance of apoptotic cells by macrophages, forming the foundation for tissue homeostasis and the resolution of inflammation.

However, the RA synovium exhibits a pronounced defect in efferocytosis, resulting in delayed clearance of apoptotic cells—particularly neutrophils—thereby precipitating secondary necrosis, the release of damage-associated molecular patterns (DAMPs), exposure of self-antigens, and chronic inflammation, ultimately establishing a vicious cycle. Preclinical studies targeting this mechanism have demonstrated that either activating TAM receptors or pro-resolving lipid mediators to enhance efferocytic signaling, or blocking its inhibitory pathways, can significantly attenuate inflammation and protect joints.