Lung type 2 immunity protects against pathogenic infection, but its dysregulation causes asthma. Although it has long been observed that symptoms of asthmatic patients often become exaggerated following food intake, the pathophysiological mechanism underlying this postprandial phenomenon is incompletely understood. Here, we report that lung type 2 immunity in mice is enhanced after feeding, which correlates with parasympathetic activation. Also, local parasympathetic innervations exhibit spatial engagement with such immune responses mediated by group 2 innate lymphoid cells (ILC2s). Pharmacologic or surgical blockage of parasympathetic signals diminishes lung type 2 immunity. Conversely, chemogenetic manipulation of parasympathetic inputs and their upstream neurocircuit is sufficient to modulate those immune responses. We then show that the cholinergic receptor muscarinic 4 (Chrm4) for the parasympathetic neurotransmitter acetylcholine is expressed in mouse or human lung ILC2s, and the Chrm4 deletion mitigates ILC2-mediated lung inflammation. These results have revealed a critical neuroimmune function of the gut-brain-lung reflex.
Keywords: Chrm4; ILC2s; cholinergic receptor muscarinic 4; food intake; group 2 innate lymphoid cells; lung type 2 immunity; parasympathetic signal.
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