A pulmonary innate lymphoid cell-driven serotonergic neuroimmune axis orchestrates airway hyperreactivity and cough hypersensitivity.

Pulmonary group 2 innate lymphoid cells (ILC2) drive airway hyperreactivity and cough hypersensitivity by expressing Tph1 and releasing serotonin after IL-33 stimulation.

• Why it matters: Asthma involves airway hyperreactivity and chronic cough, often worsened by viruses or allergens, but the immune-to-serotonin neuroimmune pathways remain unclear.
• What they did: ILC2s expressed Tph1 and released serotonin via C/EBPβ-dependent transcription after IL-33; Tph1 deficiency and adoptive transfer showed ILC2-derived serotonin amplified type 2 cytokines through 5-HT2A–NF-κB, worsening AHR in respiratory syncytial virus-driven asthmatic models. Engineered viral tools linked ILC2-derived serotonin to vagal sensory neuron sensitization via 5-HT3A.
• The result: In asthma patients, TPH1 and plasma serotonin were elevated and correlated with type 2 cytokines, supporting an ILC2-driven serotonergic circuit as a therapeutic target.

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