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A7596 - Dissecting the Role of Pulmonary Neuroendocrine Cells in Lung Immune Responses
Author Block: X. Sun, P. Sui; Pediatrics, University of California, San Diego, San Diego, CA, United States.
RATIONALE: At resting, an average person inhales/exhales 5-8 litters of air. The air may vary in oxygen content, carry allergen, pollutants or pathogens. To address how the lung senses and responds to these signals, we focused on pulmonary neuroendocrine cells (PNECs). PNECs are rare airway epithelial cells that are innervated. They can produce potent neuropeptides, neurotransmitters and amines. In vitro studies indicate that they can be stimulated to depolarize by signals such as hypoxia. However, their in vivo function remains poorly understood. METHODS: We generated mouse mutants defective in genes that are expressed in PNECs. We quantified the physiological, cellular and molecular phenotypes both at baseline as well as under allergen challenge. RESULTS: We found that mutants in which PNECs failed to clustering into neuroepithelial bodies (NEB) show increased PNEC neuropeptides and heightened baseline immune signature. We also found that mutants in which PNECs failed to form show strikingly dampened Th2 response to allergen. CONCLUSIONS: Our data provide the first in vivo demonstration that despite their rarity, PNECs act as powerful sensors on the airway. They receive environmental stimuli, translate and amplify them into specific physiological responses.