@article {45336,
	title = {Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways.},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {111},
	year = {2014},
	month = {2014 Aug 5},
	pages = {11515-20},
	abstract = {<p>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.</p>
},
	issn = {1091-6490},
	doi = {10.1073/pnas.1411032111},
	author = {Tr{\"a}nkner, Dimitri and Hahne, Nadeau and Sugino, Ken and Hoon, Mark A and Zuker, Charles}
}
