Basophils in atopic dermatitis

Atopic dermatitis (AD) or eczema is a chronic inflammatory skin disease, characterized by dysfunction of the epidermal skin barrier causing increased sensitization to environmental allergens. The resulting type 2-dominated local and systemic immune responses cause epidermal hyperplasia, dermal infiltration by T cells and eosinophilia, and elevated levels of total and allergen-specific IgE. In addition, the skin of patients with AD is often colonized with Staphylococcus aureus which correlates with diseases severity. Recent emerging studies highlight a significant role for basophils in both local and systemic responses of AD pathogenesis. Although rare in the circulation, basophils rapidly infiltrate inflamed skin, and on activation, they release IL-4 and IL-13, which are key players in the development of AD. They also secrete mediators such as histamine, leukotrienes, and IL-31 which contribute to inflammation and pruritus. Basophils also influence through their production of IL-4 T-cell polarization and B-cell class switching, supporting systemic sensitization and the development of atopic march. Basophils are gaining recognition as clinically actionable contributors to AD. The basophil activation test, which measures the activation of basophils in the blood in response to specific allergens, offers promising tools for assessing AD pathogenesis and response to treatment. In addition, therapies such as dupilumab, tralokinumab, and nemolizumab which target IL-4, IL-13, and IL-31, respectively, likely exert part of their effect by modulating basophil activity. In this review, we summarize the immunologic functions of basophils in AD pathogenesis, discuss their relevance as biomarkers and therapeutic targets, and outline future directions for integrating basophil-focused strategies in the management of patients with AD.