title: Pulmonary neuroendocrine cells function as airway sensors to control lung immune response.
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.
authors.affiliation: Laboratory of Genetics, Department of Medical Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Branchfield
authors.affiliation: Laboratory of Genetics, Department of Medical Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Nantie
authors.affiliation: Laboratory of Genetics, Department of Medical Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Verheyden
authors.affiliation: Laboratory of Genetics, Department of Medical Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Sui
authors.affiliation: Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wienhold
authors.affiliation: Laboratory of Genetics, Department of Medical Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA. xsun@wisc.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D004002:Clodronic Acid / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008171:Lung Diseases / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D055099:Neuroendocrine Cells / Q000276:immunology* / Q000378:metabolism; D009479:Neuropeptides / Q000096:biosynthesis*; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D000097905:Roundabout Proteins
chemical_list: D004002:Clodronic Acid; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins