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

Platelet-derived serotonin activates macrophage epigenetic reprogramming via TGM2, promoting type 2 airway inflammation in mice and humans.

• 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 not well known.
• What they did: Using single-cell transcriptomics of human nasal polyps and mouse models of type 2 airway inflammation, the study identified a TGM2 high macrophage population linked to eosinophilia, and demonstrated that inhibiting platelet serotonin release or TGM2 activity reduces inflammation.
• The result: The findings reveal a serotonin-TGM2-H3Q5Ser axis that couples platelet activation to macrophage epigenetic programming, offering potential therapeutic targets for airway diseases.