Platelet-derived serotonin epigenetically programs macrophage alternative activation to orchestrate type 2 airway inflammation.

Platelet-derived serotonin activates an epigenetic pathway involving TGM2 and H3Q5Ser to promote macrophage alternative activation in airway inflammation, with 50% reduction in disease severity when inhibited.

• Why it matters: Understanding how coagulation and platelet recruitment influence chronic airway diseases like eosinophilic chronic rhinosinusitis and asthma is crucial, as their roles in shaping inflammation are poorly understood.
• What they did: The study used single-cell transcriptomics of human nasal polyps and mouse models of type 2 airway inflammation, focusing on TGM2 expression, serotonin signaling, and epigenetic modifications in macrophages.
• The result: Blocking platelet serotonin release or TGM2 activity reduced airway inflammation and tissue remodeling, highlighting a novel serotonin-TGM2-H3Q5Ser axis as a promising therapeutic target for airway diseases.