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Pulmonary neuroendocrine cells function as airway sensors to control lung immune response

Science  12 Feb 2016:
Vol. 351, Issue 6274, pp. 707-710
DOI: 10.1126/science.aad7969

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Neuroendocrine cells as air sensors

Liters of air pass through the lung every minute. Signals in the atmospheric environment are processed into physiological outputs, including the immune response. Branchfield et al. show that rare airway cells called pulmonary neuroendocrine cells (PNECs) sense and respond to airborne cues (see the Perspective by Whitsett and Morrisey). Inactivating Roundabout genes in mouse PNECs prevents normal PNEC clustering and causes an increase in the production of neuropeptides, which in turn trigger a heightened immune response. Thus PNECs, despite their rarity, are sensitive and effective rheostats on the airway wall that receive, interpret, and respond to environmental stimuli.

Science, this issue p. 707; see also p. 662

Abstract

The lung is constantly exposed to environmental atmospheric cues. How it senses and responds to these cues is poorly defined. Here, we show that Roundabout receptor (Robo) genes are expressed in pulmonary neuroendocrine cells (PNECs), a rare, innervated epithelial population. Robo inactivation in mouse lung results in an inability of PNECs to cluster into sensory organoids and triggers increased neuropeptide production upon exposure to air. Excess neuropeptides lead to an increase in immune infiltrates, which in turn remodel the matrix and irreversibly simplify the alveoli. We demonstrate in vivo that PNECs act as precise airway sensors that elicit immune responses via neuropeptides. These findings suggest that the PNEC and neuropeptide abnormalities documented in a wide array of pulmonary diseases may profoundly affect symptoms and progression.

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