Current therapies for asthma and COPD primarily include corticosteroids, bronchodilators, and leukotriene antagonists, but these are thought to have little impact, if any, on airway remodeling, said Dr. Croft.
Dr. Croft said emerging data on the role of the tumor necrosis factor (TNF) super family of molecules in fueling inflammatory diseases, including his own finding on OX40 Ligand and its receptor's action in triggering inflammation in asthma, prompted him to take a close look at fellow TNF molecule, LIGHT. "We hypothesized that LIGHT might be involved in driving aspects of lung inflammation or have a role in lung dysfunction that was different than our previous findings on OX40L," he said. "As we were undertaking our studies, a report found that increased sputum LIGHT levels in people with asthma correlated with decreased lung function, which was in line with our thinking."
Using two mouse models of chronic asthma and a therapeutic blocking strategy, Dr. Croft said he and his team "demonstrated a direct role for LIGHT in promoting and controlling the extent of remodeling in the lung."
In a related finding, published March 14 in the Journal of Experimental Medicine, Dr. Croft also showed a connection between LIGHT and T cell-fueled inflammation that contributes to other aspects of asthmatic disease. "We showed that blocking LIGHT binding to one of its receptors, named the herpesvirus entry mediator, reduced the ability of T lymphocytes, induced with a model allergen, to survive long-term. This strongly curtailed lung inflammation associated with asthma when the allergen was subsequently inhaled," he said. The findings we
|Contact: Bonnie Ward|
La Jolla Institute for Allergy and Immunology