Efferocytosis and Apoptotic Cell Clearance Mechanisms

Efferocytosis is the specialised process by which phagocytes recognise, engulf and degrade apoptotic cells, thereby maintaining tissue homeostasis and preventing deleterious inflammation. This multistep clearance mechanism is orchestrated through initial release of “find-me” signals by dying cells, exposure of “eat-me” signals such as phosphatidylserine on the apoptotic cell surface, and engagement of a diverse repertoire of phagocytic receptors and bridging molecules. Following internalisation, the apoptotic cargo is trafficked to phagolysosomes for enzymatic degradation, accompanied by anti-inflammatory cytokine production and metabolic reprogramming of the phagocyte. Efficient efferocytosis underpins developmental remodelling, resolution of acute inflammation and prevention of chronic inflammatory and autoimmune disorders. Conversely, defective clearance contributes to persistent inflammation, autoimmunity, atherosclerosis and aspects of cancer progression, while cancer cells may exploit efferocytic pathways to foster an immunosuppressive microenvironment. Understanding the molecular machinery and modulation of efferocytosis has become central to the design of therapies targeting inflammatory diseases, ageing-related pathologies and tumour immunity.

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Efferocytosis and Apoptotic Cell Clearance Mechanisms publication trend

The graph below shows the total number of articles in efferocytosis and apoptotic cell clearance mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Efferocytosis: The active clearance of apoptotic cells by professional or non-professional phagocytes, combining recognition, engulfment and degradation.

Apoptosis: Programmed cell death featuring cell shrinkage, chromatin condensation and membrane blebbing, typically immunologically silent.

Phagocyte: A cell (for example, macrophage, dendritic cell) specialised in engulfing and digesting cellular debris and pathogens.

Find-me signals: Chemotactic factors released by apoptotic cells to recruit phagocytes.

Eat-me signals: Surface markers (notably phosphatidylserine) exposed on apoptotic cells to trigger phagocytic recognition.

Phagolysosome: Intracellular organelle formed by fusion of a phagosome with a lysosome, where ingested material is degraded.

DAMPs (Damage-Associated Molecular Patterns): Endogenous molecules released from dying cells that can provoke inflammation if not promptly cleared.

References

1. After cell death: the molecular machinery of efferocytosis. Experimental & Molecular Medicine (2023).
2. Targeting Efferocytosis in Inflammaging. The Annual Review of Pharmacology and Toxicology (2023).
3. Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer. Cell Death & Differentiation (2016).
4. Phagocytosis of Apoptotic Cells in Resolution of Inflammation. Frontiers in Immunology (2020).