Basophils prime group 2 innate lymphoid cells for neuropeptide-mediated inhibition [RNA-seq]
Type 2 cytokine responses promote parasitic immunity and initiate tissue repair but, can also result in immunopathologies when not properly restricted. Basophilia is recognized as a common feature of type 2 inflammation, however, the roles basophils play in regulating these responses remain unknown. Here, we demonstrate that helminth-induced ILC2 responses are exaggerated in the absence of basophils, resulting in increased inflammation and diminished lung function. Additionally, we show that ILC2s from basophil-depleted mice express reduced levels of the receptor for the neuropeptide, neuromedin B (NMB). Critically, NMB stimulation inhibited ILC2 responses from control but not basophil-depleted mice, and basophils were sufficient to directly enhance NMB receptor (NMBR) expression on ILC2s. These studies suggest that basophils prime ILC2s to respond to neuron-derived signals necessary to maintain tissue integrity. Further, these data provide mechanistic insight into the functions of basophils and identify NMB as a potent inhibitor of type 2 inflammation. Overall design: Lung-resident ILC2s were sort-purified from WT mice infected with Nippostrongylus brasiliensis 7 days prior and treated with vehicle or recombinant Neuromedin B (NMB) for 24 hours. 3 biological replicates per experimental group were used from ILC2s sort-purified from 5 mice per biological sample.