Summary:
This study is a narrative review examining the role of mast cells in atopic dermatitis (AD), a chronic inflammatory skin disease driven by immune dysregulation, skin barrier impairment, and environmental factors. Mast cells are abundant in the skin and contribute to AD through both IgE-dependent and IgE-independent activation pathways. When activated, they release histamine and inflammatory cytokines, which promote inflammation, disrupt epidermal barrier function, and induce the sensation of itch. Mast cells also interact closely with nerves and other immune cells, including T cells, dendritic cells, eosinophils, and B cells, amplifying and maintaining chronic disease states. The review highlights that mast cell involvement in AD is supported in the literature, with studies showing reduced disease severity in the absence of mast cells and restoration of symptoms following mast cell reintroduction. These findings inform the development of targeted therapies aimed at mast cell pathways. Overall, this study positions mast cells as central regulators of inflammation and itch in AD and highlights their importance as therapeutic targets for improving disease control and patient outcomes.
Abstract:
Mast cells play a critical role in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disease characterized by itch, eczema, and barrier dysfunction. These immune cells are abundant in the skin and are activated in response to allergens, irritants, and microbial products. Upon activation, mast cells release a variety of mediators, including histamine, proteases, cytokines, and chemokines, which contribute to the inflammation and pruritus observed in AD. Recent studies have highlighted the importance of mast cell-derived IL-4, IL-13, and IL-31 in promoting Th2-type immune responses and itch sensation. Moreover, interactions between mast cells and sensory neurons may further exacerbate neuroimmune inflammation. Mast cells also influence skin barrier integrity by modulating keratinocyte function and disrupting tight junctions. Their numbers and activation state are often elevated in AD lesions, correlating with disease severity. Targeting mast cell activation or blocking their mediators has shown promise in preclinical models, offering potential therapeutic strategies. Overall, mast cells are increasingly recognized as key contributors to the initiation and amplification of AD, making them an important focus for understanding disease mechanisms and developing new treatments.
Article Publication Date: 30/09/2025
DOI: 10.3389/falgy.2025.1668742
