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Pulmonary neuroendocrine cells amplify allergic asthma responses

Sui, P;Wiesner, DL;Xu, J;Zhang, Y;Lee, J;Van Dyken, S;Lashua, A;Yu, C;Klein, BS;Locksley, RM;Deutsch, G;Sun, X;

Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells whose function is poorly understood. Here we show that Ascl1-mutant mice which have no PNECs exhibit severely blunted mucosal type 2 response in models of allergic asthma. PNECs reside in close proximity to group 2 innate lymphoid cells (ILC2s) near airway branch points. PNECs act through calcitonin gene-related peptide (CGRP) to stimulate ILC2s and elicit downstream immune responses. In addition, PNECs act through neurotransmitter gamma-aminobutyric acid (GABA) to induce goblet-cell hyperplasia. The instillation of a mixture of CGRP and GABA in Ascl1-mutant airways restored both immune and goblet-cell responses. In accordance, lungs from human asthmatics show increased PNECs. These findings demonstrate that the PNEC-ILC2 neuroimmunological modules function at airway branch points to amplify allergic asthma responses. Copyright 2018, American Association for the Advancement of Science.