It has long been suspected that something else is at play in asthma sufferers other than an overactive immune system, especially since treatments that dampen the immune response and reduce inflammation have variable success rates in those with this chronic disease. Now, a new mouse study has found that a specific bundle of sensory neurons mediates the hyperreactive airway responses. The study has been published in Proceedings of the National Academy of Sciences.
Asthma is an inflammatory respiratory disease that affects over 200 million people worldwide and is responsible for around 250,000 deaths each year. Sufferers have hyperreactive airways and thickened lung walls with excess mucus. The disease is characterized by acute attacks in which the airways constrict even further, which can be triggered by a variety of things such as pollen, dust and exercise.
While it is known that the immune system facilitates the inflammatory response to these triggers, researchers had their suspicions that a population of sensory neurons that are associated with the vagus nerve, the vagal ganglia, also play a role. These neurons are known to moderate respiratory responses such as coughing.
To find out if this is true, researchers from the Howard Hughes Medical Institute used mouse models of asthma that experience asthmatic-like attacks when exposed to ovalbumin, or egg white protein. They then selectively inactivated various neuronal populations in these mice based on gene expression.
They found that with the exception of one group, all the mice experienced airway constriction upon exposure to ovalbumin. The asymptomatic mice were a group in which neurons expressing a receptor known as transient receptor potential vallinoid 1 (TRPV1) were inactive. Although the mice didn’t present physical asthma-like symptoms, their immune systems reacted strongly to the allergen.
Furthermore, when the researchers stimulated this population of cells the mice experienced dramatic airway constrictions, even when they weren’t exposed to ovalbumin. However, this didn’t happen in mice that were not allergic to ovalbumin.
It is known that a molecule called sphingosine-1-phosphate is released by immune cells within the lungs of asthmatics. When the researchers stimulated the sphingosine-1-phosphate receptors, the TRPV1-expressing neurons became activated, even without exposure to ovalbumin, and airway constrictions were stimulated. This suggests that lung inflammation releases molecules that are capable of sensitizing these sensory neurons, mediating asthma attacks.
While this research is certainly informative, the mice do not actually develop asthma, meaning that they are not ideal disease models. However, if the findings are true for humans, it could possibly lead to the development of novel asthma treatments that are able to reverse the hyperreactivity in asthma sufferers. For example, researchers could start by developing drugs that target TRPV1 or the sphingosine-1-phosphate receptor; an idea that has been previously suggested.
[Header image "Ventilation," by Lily, via Flickr, used in accordance with CC BY-NC-SA 2.0]