Study reveals conserved EGFR signaling mechanism in how immune cells recognize and clear dying cells
Researchers found that EGFR signaling plays a critical role in efferocytosis—the process by which immune cells recognize and clear apoptotic (dying) cells—across evolutionarily distant organisms including C. elegans and zebrafish. The study shows that dying cells secrete EGF ligand, which acts as a recognition signal that activates phagocytes to engulf them. This discovery suggests an evolutionarily conserved mechanism that could have implications for understanding inflammation, immune function, and diseases where cell clearance is impaired.
A new preprint study demonstrates that EGFR (epidermal growth factor receptor) signaling is both necessary and sufficient for efficient efferocytosis in two different phagocyte types: gonadal sheath cells in C. elegans and microglia in zebrafish larvae. In C. elegans, loss of the EGFR gene LET-23 or its downstream effector MPK-1/ERK impairs recognition and degradation of apoptotic germ cells, while apoptotic germ cells secrete the EGF ligand LIN-3 to promote their own engulfment. Notably, overexpressing EGF in non-apoptotic cells is sufficient to trigger their engulfment, indicating EGF functions as an independent engulfment signal. In zebrafish, EGFR inhibition reduces microglial motility and corpse clearance, and ectopic EGF sources attract microglia. The findings suggest EGFR signaling controls an evolutionarily conserved module for coordinating recognition and processing of dying cells across different phagocyte types.
What's missing
The study's limitations and open questions include: whether this mechanism extends to mammalian phagocytes (macrophages, dendritic cells); the full molecular cascade downstream of EGFR activation; whether other ligands or signals cooperate with EGF in natural efferocytosis; and the physiological consequences of impaired EGFR-mediated efferocytosis in vivo beyond the tissues examined.
What different sources said
- bioRxivCenter
Conserved role of EGFR signaling in apoptotic cell recognition and processing across different phagocytes
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