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Pulmonary neuroendocrine cells amplify allergic asthma responses.

ABSTRACT: Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells whose function is poorly understood. Here we show that Ascl1-mutant mice that 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 the neurotransmitter ?-aminobutyric acid (GABA) to induce goblet cell hyperplasia. The instillation of a mixture of CGRP and GABA in Ascl1-mutant airways restores 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.

SUBMITTER: Sui P

PROVIDER: S-EPMC6387886 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Pulmonary neuroendocrine cells amplify allergic asthma responses.

Sui Pengfei P Wiesner Darin L DL Xu Jinhao J Zhang Yan Y Lee Jinwoo J Van Dyken Steven S Lashua Amber A Yu Chuyue C Klein Bruce S BS Locksley Richard M RM Deutsch Gail G Sun Xin X

Science (New York, N.Y.) 20180329 6393

Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells whose function is poorly understood. Here we show that <i>Ascl1</i>-mutant mice that 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 the ...[more]

PMID: 29599193

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