Sensory Neuron and Mast Cell Interaction in Itch Responses of Recessive Dystrophic Epidermolysis Bullosa
Session Number
3
Advisor(s)
Emmy Lev, Luwam Hailu, Matthew Hildreth, Iris Bai, Grace Lank, Lynna Yang, Elizabeth Xu, Sultan Elhaj, Brenda Abreu Molnar, Bryan Enriquez, Ziyou Ren, Nihal Kaplan, Amy Paller, Northwestern University Feinberg School of Medicine
Discipline
Medical and Health Sciences
Start Date
15-4-2026 2:15 PM
End Date
15-4-2026 3:00 PM
Abstract
Recessive dystrophic epidermolysis bullosa (RDEB) is a skin disorder caused by pathogenic variants in the COL7A1 gene, resulting in the loss of functional collagen VII proteins, which anchor the epidermis to the dermis. Without these fibrils, the skin is fragile and blisters easily, leading to severe pain, chronic wounds, and increased infection risk. However, there are no effective treatments for these symptoms. RDEB patients show reduced intraepidermal nerve-fiber density (IENF) and increased mast cell count. Our preliminary data show overall IENF loss but increased mast cells and Mas-related G-protein-coupled receptor D (MrgprD)-expressing neurons. While MrgprD-expressing neurons elicit pain- and itch-related behaviors, the role of MrgprD nerves in RDEB remains poorly studied. We hypothesized that chronic skin injury in RDEB promotes increased MrgprD nerve density and enhanced neuroimmune interaction with mast cells, which contributes to itch and pain. Using an RDEB mouse model with fluorescently labeled MrgprD⁺ nerves, tissue sections were immunostained with an anti-tryptase antibody to identify mast cells. RDEB mice showed increased MrgprD⁺ IENF (18.3%, p = 0.04) and a 473% reduction in the distance between MrgprD⁺ nerves and mast cells (p = 1.85×10⁻⁵), suggesting these neuroimmune interactions may contribute to persistent itch and pain in RDEB.
Sensory Neuron and Mast Cell Interaction in Itch Responses of Recessive Dystrophic Epidermolysis Bullosa
Recessive dystrophic epidermolysis bullosa (RDEB) is a skin disorder caused by pathogenic variants in the COL7A1 gene, resulting in the loss of functional collagen VII proteins, which anchor the epidermis to the dermis. Without these fibrils, the skin is fragile and blisters easily, leading to severe pain, chronic wounds, and increased infection risk. However, there are no effective treatments for these symptoms. RDEB patients show reduced intraepidermal nerve-fiber density (IENF) and increased mast cell count. Our preliminary data show overall IENF loss but increased mast cells and Mas-related G-protein-coupled receptor D (MrgprD)-expressing neurons. While MrgprD-expressing neurons elicit pain- and itch-related behaviors, the role of MrgprD nerves in RDEB remains poorly studied. We hypothesized that chronic skin injury in RDEB promotes increased MrgprD nerve density and enhanced neuroimmune interaction with mast cells, which contributes to itch and pain. Using an RDEB mouse model with fluorescently labeled MrgprD⁺ nerves, tissue sections were immunostained with an anti-tryptase antibody to identify mast cells. RDEB mice showed increased MrgprD⁺ IENF (18.3%, p = 0.04) and a 473% reduction in the distance between MrgprD⁺ nerves and mast cells (p = 1.85×10⁻⁵), suggesting these neuroimmune interactions may contribute to persistent itch and pain in RDEB.