With more than 300 million people around the world estimated to suffer from asthma, and numbers increasing, scientists still don't fully understand the condition. They know that too much of a protein called mucin causes the lungs' airways to close, triggering an asthma attack, but until now, the mechanism behind this was unknown. Researchers from Houston Methodist Research Institute believe the answer lies in how two molecules communicate.

In the immune system, T helper cells help immune cells recognize and fight toxins by secreting a protein called interleukin 9 (IL-9). However, when they become hyperactive, as is the case in asthma sufferers, they secrete a molecule called OX40 that triggers the production of too much IL-9. This, in turn, results in too much mucin being produced by the mucous membranes in the airways, restricting the flow of air and causing the shortness of breath felt during an asthma attack.

"In essence, OX40 activates the IL-9 gene in T helper cells, leading to the overproduction of IL-9 through a powerful molecular machinery of super-enhancers that regulate gene expression," says Dr. Xian C. Li, the director of the Immunobiology & Transplant Science Center at Houston Methodist Research Institute.

Super-enhancers are regions of DNA that decide which genes become active, and by using chemical inhibitors to block those super-enhancers responsible for the hyperactivity of T helper cells, the researchers were able to prevent the overproduction of IL-9, and therefore also of mucin.

"If we can do this and develop better and more specific drugs to selectively stop super-enhancers, asthmatic patients may never have to struggle for air again," says Li.

The researchers are hoping they will be able to help asthma sufferers breathe easy again by preventing the protein build-up in its beginning stages. By understanding the mechanisms behind mucin buildup, their research holds the potential for the development of a new class of drugs to treat asthma.

"Finding new approaches to target and block super-enhancers may provide a new means of treatment for asthma patients that is likely to be more efficacious than the standard of care, which is now steroids," says Li.

This study was published in the Journal of Experimental Medicine.

Source: Houston Methodist Research Institute

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