Researchers find missing piece of the asthma puzzle: New study reveals how the inflammatory LIGHT protein leads to airway remodeling and long-term breathing issues

An inflammatory molecule called LIGHT, appears to be the cause of life-threatening airway damage in patients with severe asthma. According to the new research from scientists at La Jolla Institute for Immunology (LJI), therapeutics to stop LIGHT (which is related to tumor necrosis factor) could reverse airway and lung damage in patients — and potentially offer a long-term treatment for asthma.

“This is a very, very significant finding,” says LJI Professor Michael Croft, Ph.D., senior author of the new study and member of the LJI Center for Autoimmunity and Inflammation. “This research gives us a better understanding of the potential of therapeutic targeting of LIGHT and what we might do to relieve some of the symptoms and some of the inflammatory features seen in patients who have severe asthma.”

This research was published recently in the Journal of Allergy and Clinical Immunology. The study included experiments with both mouse and human tissues and was spearheaded by LJI Instructor Haruka Miki, M.D., Ph.D.

Croft’s team has studied LIGHT for more than a decade. The LIGHT protein is a type of inflammatory “cytokine” produced by the immune system’s T cells. T cells normally fight disease, but in asthma, T cells overreact to environmental triggers and flood the airways with LIGHT and other inflammatory cytokines. Researchers have developed therapies to block the activity of some of the other harmful cytokines made by T cells, but these therapies aren’t effective for many with severe asthma.

LIGHT can be found elevated in the sputum of asthmatic patients with severe disease, and Croft’s previous work showed that LIGHT is essential in a process called tissue “remodeling,” where the lungs and airways grow thicker following an asthma attack. These thicker airways can leave a person with long-term breathing problems.

“Current treatments for asthma are mainly to suppress symptoms and subdue allergic inflammation. No treatment has been developed to fundamentally cure asthma,” says Miki. “Even when inflammation is suppressed by current treatments, underlying airway hyperresponsiveness and airway tissue changes (airway remodeling) often remain, especially in severe asthma.”

Even though they knew LIGHT was involved in this remodeling, the researchers did not know whether LIGHT directly affects the smooth muscle tissue that lines the major airways of the lungs. These cells increase in number and size in moderate and severe asthmatics, which is thought to be a primary cause of loss of lung function.

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