Blocking the action of calcium signals in immune cells suppresses the most common form of asthma, but without compromising the body’s defenses against flu viruses, a new study finds.
Led by researchers at NYU Grossman School of Medicine, experiments showed that removing the gene for a calcium channel — specifically the calcium release-activated calcium (CRAC) channel made up of ORAI1 proteins — thoroughly reduced asthmatic inflammation in the lungs of mice caused by house dust mite feces, a common cause of allergic asthma. Blocking signals sent through this channel with an investigational new drug called a CRAC channel inhibitor had a similar effect.
The study revolved around the use of charged particles, mainly calcium, by human cells to send signals and flip biological switches. When triggered–whether by viral proteins or allergens — immune cells called T cells open channels in their outer membranes, letting calcium rush in to turn on signaling pathways that control cell division and secretion of cytokine molecules that help T cells communicate with other immune cells.
Past work had found that CRAC channels in T cells regulate their ability to multiply into armies of cells designed to fight infections caused by viruses and other pathogens.
Published online in Science Advances on October 7, the new study showed that the CRAC channel inhibitor reduced allergic asthma and mucus build-up in mice without sabotaging their immune system’s ability to fight influenza, a main worry of researchers seeking to tailor immune-suppressing drugs for several applications.
“Our study provides evidence that a new class of drugs that target CRAC channels can be used safely to counter allergic asthma without creating vulnerability to infections,” says senior study author Stefan Feske, MD, the Jeffrey Bergstein Professor of Medicine in the Department of Pathology at NYU Langone Health. “Systemic application of a CRAC channel blocker specifically suppressed airway inflammation in response to allergen exposure.”
About 25 million Americans suffer from asthma, with repeated episodes of wheezing, breathlessness, chest tightness, and coughing, according to the Centers for Disease Control and Prevention. The majority of those have asthma related to inhaled allergens, say the study authors.
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