Cell protein triggers reactions by binding with house dust mite allergens
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Key takeaways:
- LMAN1 binds with house dust mite allergens, triggering inflammation.
- This binding depends on specific mannose sugar structures on house dust mite allergens.
- Mannose sugars also can modify other allergens.
A cell protein known as LMAN1 plays a role in responses to house dust mite, opening potential avenues for new treatments for these and other allergies, according to a study published in Cell Reports.
Previously, researchers had not known that LMAN1 had any part in allergen responses, Justine T. Tigno-Aranjuez, PhD, assistant professor, immunity and pathogenesis division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, and colleagues wrote.
LMAN1, which transports other proteins inside and outside the cell, is considered a cargo receptor. But using LRC-TriCEPS (Dualsystems Biotech AG), which identifies receptors in cells, the researchers found that house dust mite allergens and LMAN1 can bind together on the cell surface to cause an inflammatory or allergic reaction.
“That is part of what we are trying to find out. We know it binds allergens. We know expression of LMAN1 seems to be reduced on the surface of specific immune cells of allergic asthmatics. However, we are still trying to understand exactly what it does,” Tigno-Aranjuez told Healio.
“Our data suggests it inhibits inflammatory signaling promoted by allergens, but we have to confirm this in vivo,” Tigno-Aranjuez continued. “Additionally, outcomes might be different depending on the cells we focus on — for example, airway epithelial cells vs. dendritic cells.”
This binding depends on specific mannose sugar structures on house dust mite allergens, the researchers said, adding that this discovery has potential to impact treatment since pollen, fungi and other common allergens are mannosylated, or modified by the addition of mannose sugars.
“Most current treatments available treat the symptoms of allergies after the fact, rather than preventing them,” Eric Eraso, spokesperson for University of Central Florida College of Medicine, told Healio.
Meanwhile, immunotherapies that induce tolerance to these allergens in patients often take 3 to 5 years and may lead to anaphylaxis and other severe side effects, Eraso continued.
“They are also specific to the exact allergen one is sensitive to rather than being flexible to many allergens,” he said.
But if Tigno-Aranjuez and her colleagues can show that LMAN1 is a sensor for multiple allergens and that they can develop therapy that mimics what LMAN1 is doing, Eraso said, there would be no need to make treatment specific to one allergen.
“We could potentially make a therapy that applies to many of the most common allergens at once,” he said.
In other words, Eraso said, LMAN1 binds to the sugars in house dust mite allergens. The researchers hypothesize that other common allergens such as pollen that have these same sugars also would bind to LMAN1.
“This would mean that a potential treatment that addresses this commonality could potentially be used for a wide variety of allergens,” he said. “This research could be a major building block that leads to more preventative and broadly applicable allergy treatments for the millions who experience symptoms every year.”
The NIH has awarded Tigno-Aranjuez a $1.5 million grant to explore whether LMAN1 has a part in the expression of other mannosylated allergens.
“Dr. Tigno-Aranjuez and her team are now conducting research to confirm their hypothesis that other mannosylated allergens, such as pollen, are also recognized by LMAN1,” Eraso said. “If true, this could have broad implications in future therapies for many of the most common allergens.”