Penn Dental Medicine Researchers Exploring the Mysteries of Mast Cells, Inflammation

PHILADELPHIA, July 31, 2024 /PRNewswire/ -- Mast cells are found throughout the body close to blood vessels and are packed with granules containing the immune signaling compound histamine, and enzymes that attack pathogens and promote white blood cell recruitment. When triggered by a perceived threat, mast cells expel their contents. This activity protects against infection and aids healing, but it has also made mast cells infamous for driving allergic asthma and inflammatory skin disorders, such as rosacea and contact dermatitis. 

Despite their prominence, few researchers study these scarce and difficult-to-work-with cells. Hydar Ali, a professor in the Department of Translational Sciences at Penn Dental Medicine, belongs to a select group who focus on mast cells. His research explores how they function to protect the body and how things can go wrong. 

"These cells are relatively poorly understood, and yet we've been able to identify some of the most sought-after molecular targets to affect diseases like allergies and asthma that have the potential to kill," Ali says. 

He and his colleagues discovered a receptor, known as MRGPRX2, that only appears on mast cells. This research led them to find that small proteins called antimicrobial peptides could activate mast cells through MRGPRX2 to harness their protective function and help clear pathogens. In the context of an allergic response, however, he has shown that this receptor drives problematic inflammation. 

"It's two sides of the same coin," Ali says.

More recently, his team has investigated mast cells' role in systemic allergic reactions that can lead patients to stop using the multiple sclerosis drug glatiramer acetate. Their experiments demonstrated that this medication activates MRGPRX2 receptors causing mast cells to expel histamine and their other contents, results suggesting MRGPRX2 inhibitors could treat these reactions and help patients remain on the medication. 

His lab is also investigating this receptor's role in periodontal disease, an inflammatory condition that damages the gums and connective tissue of the mouth. Their experiments have shown, for example, that mast cells expressing MRGPRX2 become more abundant in chronic periodontitis, the more severe form of the condition. Ultimately, he hopes to study the potential for MRGPRX2 blockers to reduce inflammation in periodontitis. 

Media Contact: Beth Adams, [email protected]

SOURCE PENN DENTAL MEDICINE