Science 359, 1056–1061 (2018)

Group 2 innate lymphoid cells (ILC2s) protect mucosal barriers against helminths, allergens and other noxious stimuli. In Science, Moriyama et al. reveal a negative regulatory interaction between adrenergic neurons and ILC2s that reside in close proximity in the gut and lungs. Human and mouse ILC2s express β2-adrenergic receptors (β2-ARs) that respond to norepinephrine and other β2-AR agonists. Mice that lack β2-AR expression have a frequency of ILC2s similar to that of wild-type mice at steady state but exhibit enhanced eosinophilia, mucus production and worm expulsion after helminth infection. Agonist stimulation of β2-AR signaling suppresses the infection-induced proliferation of ILC2s and thereby diminishes type 2 immune responses. Thus, adrenergic neuron–ILC2 interactions are tuned to avoid over-exuberant type 2 inflammatory responses.