Pulmonary neuroendocrine cells amplify allergic asthma responses

作者：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^*

来源：Science, 2018, 360(6393): 1086-+.

DOI：10.1126/science.aan8546

• INNATE LYMPHOID-CELLS
• NEUROEPITHELIAL BODIES
• MUCUS OVERPRODUCTION
• NEURONS
• INNERVATION
• GABA
• DIFFERENTIATION
• INFLAMMATION
• EPITHELIUM
• MIGRATION

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 gamma-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.

• 出版日期2018-6-8
• 单位上海交通大学