efferocytosis

Efferocytosis is the process by which phagocytes, principally macrophages and dendritic cells, clear apoptotic cells from tissues. It is essential for maintaining tissue homeostasis, resolving inflammation, and preventing autoimmune responses. During apoptosis, cells expose phosphatidylserine and other signals on their outer membrane, which marks them for removal.

Recognition and engulfment involve multiple receptors and bridging molecules. Phagocytes detect phosphatidylserine directly through receptors such as TIM4 and, in conjunction with integrins, through bridging proteins like MFG-E8 (lactadherin) and Gas6 or Protein S that link apoptotic cells to TAM receptors (MerTK, Axl, Tyro3). The CD47–SIRPα interaction on viable cells acts as a “don’t eat me” signal and can modulate efferocytosis. Engulfment then proceeds via cytoskeletal remodeling to form an efferosome, which fuses with lysosomes for degradation and recycling of cellular components.

The outcome of efferocytosis is typically anti-inflammatory and pro-resolving. Phagocytes release anti-inflammatory cytokines such as IL-10 and TGF-β and reduce production of pro-inflammatory mediators, promoting tissue repair and tolerance. Efferocytosis can also influence dendritic cell maturation and, in some contexts, shaping adaptive immune responses.

Clinical relevance and pathology: Efficient efferocytosis maintains tissue integrity, while impaired clearance of dying cells is linked to chronic inflammation, autoimmunity (for example, systemic lupus erythematosus), and atherosclerosis. Defects in efferocytosis can contribute to necrotic tissue progression and plaque instability, whereas certain cancers may alter efferocytic pathways to influence tumor-immune interactions. In development and tissue remodeling, timely efferocytosis supports orderly morphogenesis and healing.