Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways.

Authors: Dimitri Tränkner, Nadeau Hahne, Ken Sugino, Mark A Hoon, Charles Zuker

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2014 Aug 5 , 111, 11515-20

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25049382

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.