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Science. 2018 Jun 8;360(6393). pii: eaan8546. doi: 10.1126/science.aan8546. Epub 2018 Mar 29.

Pulmonary neuroendocrine cells amplify allergic asthma responses.

Author information

1
Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA.
2
Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
3
Department of Pediatrics, University of Wisconsin-Madison, Madison, WI 53706, USA.
4
Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
5
Zhiyuan College, Shanghai JiaoTong University, Shanghai, China.
6
Department of Laboratories, Seattle Children's Hospital, University of Washington, Seattle, WA 98105, USA.
7
Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA. xinsun@ucsd.edu.

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 γ-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.

PMID:
29599193
PMCID:
PMC6387886
DOI:
10.1126/science.aan8546
[Indexed for MEDLINE]
Free PMC Article

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