Ferroptosis as an Emerging Therapeutic Target in Allergic Diseases

Allergic diseases-including allergic asthma, allergic rhinitis, and atopic dermatitis-pose an escalating global health challenge. While traditionally viewed as type 2-driven disorders, many patients remain refractory to current therapies, highlighting the urgent need for novel mechanistic insights and therapeutic approaches. Emerging evidence implicates ferroptosis, an iron-dependent, lipid peroxidation-driven form of regulated cell death, in allergic pathogenesis. This review synthesizes current knowledge on ferroptosis in allergic diseases, emphasizing its context-dependent roles. In structural cells such as epithelial cells and keratinocytes, ferroptosis compromises barrier integrity, releases damage-associated molecular patterns (DAMPs), and propagates type 2 inflammation. Conversely, in immune cells-including eosinophils, T cells, and group 2 innate lymphoid cells (ILC2s)-dysregulated ferroptosis modulates survival and function, offering both pathogenic and therapeutic implications. Ferroptosis also influences IgE production through B-cell survival and class-switching, and emerging data suggest ferroptotic signals affect mast cell activation and IgE-mediated responses, linking this pathway to humoral allergic inflammation. We further discuss therapeutic strategies that either inhibit ferroptosis to preserve tissue barriers or induce ferroptosis to eliminate pathogenic immune cells. However, the clinical translation of ferroptosis-targeting approaches remains preliminary, with most evidence derived from experimental models, warranting cautious interpretation and rigorous validation. Collectively, ferroptosis represents a mechanistically distinct and promising therapeutic target in allergic diseases, though its clinical utility awaits confirmation. Strategic, context-specific modulation of this pathway holds potential to overcome current therapeutic limitations, particularly for severe, refractory, or non-type 2 endotypes.