Extracellular vesicles presenting "don't eat me" signal limit the efferocytic capacity in lung fibrosis.

In idiopathic pulmonary fibrosis, efferocytosis is profoundly suppressed and extracellular vesicles displaying functional CD47 are robustly produced and released, limiting clearance of apoptotic fibroblasts.

• Why it matters: Efferocytosis is needed to resolve inflammation, but its direct role in resolving organ fibrosis is unclear, especially in age-driven disease.
• What they did: In aged mice with lung fibrosis, restoring efferocytosis promotes natural fibrosis resolution, which is accelerated by CD47 deficiency or macrophage metabolic alterations; pharmacologic disruption of efferocytic receptors or signaling promotes fibrosis persistence.
• The result: AMPK activation promotes fibrosis resolution by reducing inflammaging and CD47 bioavailability, reprogramming macrophages to suppress TGF-β1 and increase pro-regenerative HGF secretion.

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