Basophils in the regulation of allergies and inflammatory disorders

Basophils are rare granulocytes that were long overlooked because of their scarcity and phenotypic overlap with mast cells. Recent advances in genetic models and antibody-based depletion strategies have redefined basophils as versatile regulators of inflammation, particularly in the context of type 2 immune responses such as atopic dermatitis (AD) and allergic asthma. In patients with AD and asthma, basophils infiltrate sites of inflammation, and studies using mouse models have demonstrated their crucial roles in allergic inflammation of the skin and lungs. Emerging evidence further indicates that basophils migrate to inflamed tissues and draining lymph nodes, where they interact with a broad range of immune and non-immune cells, including macrophages, T cells, dendritic cells, innate lymphoid cells, endothelial cells, fibroblasts, and sensory neurons. Through these interactions, basophils amplify type 2 inflammatory responses in diseases such as AD and asthma. In contrast, accumulating evidence indicates that basophils can also facilitate the resolution of both allergic and non-allergic inflammation by promoting pro-resolving macrophage programs. In addition, context-dependent roles of basophils have been described in tissue repair, fibrotic remodeling, lung emphysema, and the resolution of acute lung injury. In the first part of this review, we summarize the molecular mechanisms governing basophil activation and outline how regulation of these pathways contributes to the control of allergic inflammation. In the latter half, we provide a comprehensive overview of the context-dependent roles of basophils in inflammatory responses and outline the conceptual framework that supports therapeutic strategies targeting basophil activation or specific basophil-derived mediators.