Pulmonary neuroendocrine cells amplify allergic asthma responses

Pengfei Sui, Darin L. Wiesner, Jinhao Xu, Yan Zhang, Jinwoo Lee, Steven Van Dyken, Amber Lashua, Chuyue Yu, Bruce S. Klein, Richard M. Locksley, Gail Deutsch, Xin Sun

Research output: Contribution to journalArticle

70 Scopus citations

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 g-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.

Original languageEnglish
Article numbereaan8546
JournalScience
Volume360
Issue number6393
DOIs
StatePublished - Jun 8 2018
Externally publishedYes

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    Sui, P., Wiesner, D. L., Xu, J., Zhang, Y., Lee, J., Van Dyken, S., Lashua, A., Yu, C., Klein, B. S., Locksley, R. M., Deutsch, G., & Sun, X. (2018). Pulmonary neuroendocrine cells amplify allergic asthma responses. Science, 360(6393), [eaan8546]. https://doi.org/10.1126/science.aan8546