Pulmonary neuroendocrine cells amplify allergic asthma responses

• Published in: Science (American Association for the Advancement of Science) 2018-06, Vol.360 (6393)
• Main Authors: Sui, Pengfei, Wiesner, Darin L, Xu, Jinhao, Zhang, Yan, Lee, Jinwoo, Van Dyken, Steven, Lashua, Amber, Yu, Chuyue, Klein, Bruce S, Locksley, Richard M, Deutsch, Gail, Sun, Xin
• Format: Article
• Language: English
• Subjects: Acids; Allergens; Allergies; Allergy; Alveoli; Amines; Amphibians; Amplification; Animal models; Animals; ASCL1 protein; Asthma; Asthma - immunology; Asthma - pathology; Basic Helix-Loop-Helix Transcription Factors - deficiency; Basic Helix-Loop-Helix Transcription Factors - genetics; Calcitonin; Calcitonin gene-related peptide; Calcitonin Gene-Related Peptide - metabolism; Cell culture; Chemical sensors; Chemoreceptors; Clustering; Cytokines; Cytokines - biosynthesis; Deactivation; Dense core vesicles; Disease Models, Animal; Effectors; Epithelial cells; Epithelial Cells - immunology; Epithelial Cells - pathology; Epithelium; Feedback (Response); Female; gamma-Aminobutyric Acid - biosynthesis; gamma-Aminobutyric Acid - metabolism; Goblet Cells - pathology; House dust; Humans; Hyperplasia; Hypersensitivity; Immune response; Immune system; In vivo methods and tests; Inactivation; Interleukin 5; Lung - pathology; Lungs; Mice; Modules; Molecular chains; Mucosa; Mucous membrane; Mucus; Mutants; Neuroendocrine Cells - immunology; Neuroendocrine Cells - pathology; Neuropeptides; Neurotransmitters; Numbers; Patients; Peptides; Physiological responses; Proximity; Reptiles; Respiratory tract; Rodents; Scientific Concepts; Sensory neurons
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aan8546

Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells whose function is poorly understood. Here we show that -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 -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.