UCF Researchers’ Approach Redefines Allergy Treatment

For many years, research and treatment of allergic asthma has focused primarily on targeting pro-inflammatory cytokines in the body that cause mucus overproduction, wheezing and dyspnea in response to allergens. Commonly prescribed drugs, such as omalizumab, dupilumab, mepolizumab, and leslizumab, reduce or block various cytokines and antibodies that contribute to asthma responses, but they do so only after inflammation in the patient’s airways is sufficiently advanced. Effective.

Dr. Tigno Aranjuez wanted to find a new approach to making allergen receptors unresponsive in the first place. So she turned to her technique, called LRC-TriCEPS, which identifies receptors in cells for the common allergen house dust mite. This technique points to a cellular protein called LMAN1 that had a previously unrecognized role in the body’s allergen response.

Her findings were recently published in Cell Reports, the most influential paper ever.

“When we first made this discovery, we wanted to know, ‘What is this protein?'” What do we already know about LMAN1 as an allergen receptor? What’s interesting is that people haven’t paid much attention to this protein in terms of allergies or allergic asthma,” she said.

Until her discovery, LMAN1 was commonly known as a cargo receptor, a protein that transports other proteins in and out of cells. However, Dr. Tigno Aranjuez demonstrated that the dust mite allergen and LMAN1 can bind at the cell surface to provoke inflammatory and allergic reactions. Her research further showed that binding was dependent on the specific mannose sugar structure of the dust mite allergen. This finding holds great promise because many other common allergens, including pollen and fungi, are mannosylated or modified by the addition of mannose sugars.

“Our thinking is that this may not be limited to house dust mites alone, as many other allergens are mannosylated. It could be the body,” she explained. “If we think in terms of potential therapeutics, understanding how LMAN1 recognizes house dust mites and the consequences of that recognition could potentially apply this to many other settings. , and that’s what we’re currently trying to explore.”

The National Institutes of Health also sees potential in the UCF study, awarding Dr. Tigno Aranjuez a $1.5 million R01 grant to investigate whether LMAN1 plays a role in the expression of other mannosylated allergens. I just got it.

Dr. Tigno Aranjuez’s research on LMAN1 is being conducted in collaboration with the Cleveland Clinic. Dr. Binh Chan, associate professor at the Lerner Institute, serves as a collaborator on the study. Dr. Zhang is considered his LMAN1 expert.

“LMAN 1 is widely known as a protein involved in transporting proteins from the inside to the outside of the cell,” explained Dr. Zhang. “This study demonstrates for the first time a completely new function of LMAN1 as a receptor that transports proteins such as allergens from the extracellular to the intracellular, which may open up new therapeutic avenues.”

With hundreds of thousands of cases of allergic asthma in the United States each year, and many more cases occurring worldwide, this study represents a step forward in helping these patients.

“Asthma is so prevalent that people sometimes think, ‘We already have a lot of treatments and we’re done.’ can always be improved,” said Dr. Tigno Aranjuez. “Many treatments can only be prescribed if they meet certain clinical criteria, many are prohibitively expensive, and many are not covered by insurance. Any new treatment we can offer that has the potential to become an advancement is always a step forward.”

Dr. Tigno Aranjuez and her team are now conducting studies to confirm the hypothesis that other mannosylated allergens such as pollen are also recognized by LMAN1. If this is true, it could have far-reaching implications for future treatments for many of the most common allergens.

Dr. Tigno Aranjuez immigrated from the Philippines to the United States for graduate and doctoral studies at Case Western University in Cleveland. She joined her UCF in 2015 and is focused on researching immune signaling pathways involved in chronic inflammatory diseases such as asthma and Crohn’s disease.

/ Open to the public. This material from the original organization/author may be of the nature of its time and has been edited for clarity, style and length. Mirage.News does not take any organizational positions or positions and all views, positions and conclusions expressed herein are those of the authors only. Read the full article here.

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