Study reveals conserved EGFR signaling mechanism in how immune cells recognize and clear dying cells
Researchers have found that EGFR (epidermal growth factor receptor) signaling plays a necessary and sufficient role in efferocytosis—the process by which phagocytes recognize and clear dying cells—across two evolutionarily distant organisms, C. elegans and zebrafish. In both species, apoptotic cells appear to actively recruit phagocytes by secreting EGF ligands, and artificially supplying EGF was enough to trigger engulfment even without cell death. This suggests a conserved molecular mechanism that could have broad implications for understanding inflammation, tissue homeostasis, and diseases linked to defective corpse clearance.
A new preprint study posted to bioRxiv demonstrates that EGFR signaling is both necessary and sufficient for efficient efferocytosis in two phylogenetically distant model organisms: the nematode C. elegans and zebrafish larvae. In C. elegans, loss of the EGFR homolog LET-23 or its downstream effector MPK-1/ERK in gonadal sheath cells impaired the recognition and degradation of apoptotic germ cells, while apoptotic germ cells were shown to secrete the EGF ligand LIN-3 to promote their own engulfment. Critically, overexpressing EGF in non-apoptotic germ cells was sufficient to induce their engulfment, demonstrating that EGF can act as an independent engulfment signal decoupled from the apoptotic program itself. In zebrafish, pharmacological inhibition of EGFR reduced microglial motility, impaired recognition of apoptotic neurons, and diminished corpse clearance in the optic tectum; an ectopic EGF source similarly attracted microglia. Together, these findings propose that EGFR signaling constitutes an evolutionarily conserved efferocytosis module operating across diverse phagocyte types, with potential relevance to neuroinflammation, autoimmune disease, and other conditions where defective apoptotic cell clearance drives pathology.
What's missing
As a preprint, this work has not yet undergone peer review, so findings should be interpreted with caution. The study does not address whether EGFR-driven efferocytosis operates similarly in mammalian systems, leaving the translational relevance to human disease unestablished. It is also unclear whether EGF secretion by apoptotic cells is the primary or sole 'find-me' signal, or how it interacts with other known efferocytosis cues such as lysophosphatidylcholine or nucleotides. The sufficiency experiments (ectopic EGF triggering engulfment) raise the open question of whether this pathway could inadvertently target healthy cells in pathological contexts of elevated EGF signaling.
What different sources said
- bioRxivCenter
Conserved role of EGFR signaling in apoptotic cell recognition and processing across different phagocytes
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