title: Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways.
abstract: Asthma is a common debilitating inflammatory lung disease affecting over 200 million people worldwide. Here, we investigated neurogenic components involved in asthmatic-like attacks using the ovalbumin-sensitized murine model of the disease, and identified a specific population of neurons that are required for airway hyperreactivity. We show that ablating or genetically silencing these neurons abolished the hyperreactive broncho-constrictions, even in the presence of a fully developed lung inflammatory immune response. These neurons are found in the vagal ganglia and are characterized by the expression of the transient receptor potential vanilloid 1 (TRPV1) ion channel. However, the TRPV1 channel itself is not required for the asthmatic-like hyperreactive airway response. We also demonstrate that optogenetic stimulation of this population of TRP-expressing cells with channelrhodopsin dramatically exacerbates airway hyperreactivity of inflamed airways. Notably, these cells express the sphingosine-1-phosphate receptor 3 (S1PR3), and stimulation with a S1PR3 agonist efficiently induced broncho-constrictions, even in the absence of ovalbumin sensitization and inflammation. Our results show that the airway hyperreactivity phenotype can be physiologically dissociated from the immune component, and provide a platform for devising therapeutic approaches to asthma that target these pathways separately.
authors: Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147;
authors: Dimitri
authors: D
authors: Tränkner
authors: Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147;
authors: Nadeau
authors: N
authors: Hahne
authors: Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147;
authors: Ken
authors: K
authors: Sugino
authors: National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892; and.
authors: Mark A
authors: MA
authors: Hoon
authors: Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147;Department of Biochemistry and Molecular Biophysics,Department of Neuroscience, andHoward Hughes Medical Institute, Columbia College of Physicians and Surgeons, Columbia University, NY 10032 cz2195@columbia.edu.
authors: Charles
authors: C
authors: Zuker
mesh_terms: D000818:Animals; D001249:Asthma / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D017353:Gene Deletion; D020868:Gene Silencing; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D012137:Respiratory System / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology*; D050916:TRPV Cation Channels / Q000378:metabolism; D014630:Vagus Nerve / Q000378:metabolism / Q000473:pathology
chemical_list: D049349:Receptors, Lysosphingolipid; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse
keywords: airway inflammation; bronchospasms