Efferocytosis and Its Role in Rheumatic Diseases

Efferocytosis, the process through which phagocytes clear apoptotic cells (ACs), has rapidly emerged as an expanding field of research. This multistep process involves recognizing, binding, internalizing, and degrading ACs. Efferocytosis clears ACs, preventing their secondary necrosis, generating anti-inflammatory mediators, and promoting the resolution of inflammation. Appropriate efferocytosis is essential for preserving immune tolerance and preventing exposure to self-antigens, whereas defective efferocytosis is linked to the onset of various rheumatic diseases. Here, we review the process of efferocytosis and its implications in common rheumatic diseases. This review focuses on the role of abnormal efferocytosis in the development and progression of systemic lupus erythematosus. We also summarize recent advances in understanding efferocytosis in other rheumatic diseases, including rheumatoid arthritis (RA), Sjögren disease, antineutrophil cytoplasmic antibody-associated vasculitis, systemic sclerosis, antiphospholipid syndrome, gout, and osteoarthritis. Notably, a clinical trial investigating AC infusion for refractory RA has been proposed, highlighting the therapeutic potential of targeting efferocytosis. In addition, emerging strategies-such as liver X receptor/peroxisome proliferator-activated receptor agonists; DNase-containing nanoparticles; Tyro3, Axl, and Mer receptor agonists; and anti-CD47 antibodies-show promise, although most remain at the preclinical stage. Despite the challenges posed by the immune system's complexity and the pleiotropic functions of efferocytosis-related molecules, growing evidence supports efferocytosis as a potential therapeutic target in rheumatic diseases.