Scratching restriction attenuates type 2 immune dysregulation and skin inflammation in a mouse model of atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease marked by intense pruritus, significantly affecting patients’ quality of life. Persistent scratching perpetuates the “itch-scratch cycle,” exacerbating skin barrier dysfunction and immune dysregulation. This study investigated the impact of scratching suppression on skin inflammation, type 2 immune responses, and stress hormone levels in a mouse model of AD. Using collars to restrict scratching in AD-induced mice, we observed significant reductions in erythema, crust formation, and ear thickness, alongside histological improvements including decreased epidermal and dermal thickening and reduced eosinophil and mast cell infiltration. Scratching suppression significantly downregulated Th2 cytokines (IL-4, IL-5, IL-13), the itch-associated cytokine IL-31, thymic stromal lymphopoietin (TSLP), IL-1β, and serum IgE levels, highlighting the role of scratching in amplifying immune dysregulation. Stress hormone analyses showed that corticosterone and cortisol levels peaked transiently after collar application and normalized within four days, confirming that collar-induced stress did not confound the experimental outcomes. These findings underscore the pivotal role of scratching in AD progression, emphasizing the therapeutic potential of breaking the itch-scratch cycle to restore skin barrier integrity and attenuate systemic type 2 immunity.