Dopamine inhibits type 2 innate lymphoid cell-driven allergic lung inflammation via dampening mitochondrial activity

Neuroimmune interactions are critical regulators of tissue homeostasis and allergic inflammation, and group 2 innate lymphoid cells (ILC2s) have emerged as an important cell type for mediating these interactions. Here, we identified that the abundance of dopamine (DA) was negatively correlated with the number of circulating ILC2s and lung function in human. Dopamine potently suppressed lung ILC2 responses in mice, which was dependent on the expression of dopamine receptor DRD1. Correspondingly, the local ablation of dopaminergic neurons further augmented ILC2 responses and aggravated allergic lung inflammation. Transcriptome and metabolic analyses revealed that dopamine impaired oxidative phosphorylation (OXPHOS) pathway in ILC2s. Augmentation of OXPHOS activity with oltipraz antagonized the inhibitory effects of dopamine. Finally, the local administration of dopamine dramatically alleviated allergen-induced ILC2 responses and airway inflammation. Our work highlights a model where dopamine is critical for suppressing ILC2 responses and maintaining homeostasis of type 2 immune machinery in lung.