From skin to lung: basophil-mediated spread of allergic diseases.

Basophils, the rarest type of granulocytes in peripheral blood, have emerged as important orchestrators of type 2 immune responses, including allergic inflammation. They were long considered merely as mast cell-related effector cells in IgE-mediated responses. However, they are increasingly recognized as critical orchestrators of type 2 immune responses and contributors to allergic disease pathogenesis. As significant producers of cytokines, chemokines, and eicosanoids, they are widely acknowledged as key modulators of dendritic cell (DC) function, innate lymphoid cell type 2 (ILC2) activity, and T helper 2 (Th2) cell differentiation, impacting both skin and lung inflammation. Human studies of atopic dermatitis (AD) have documented basophil infiltration within inflamed lesions, often concurrent with eosinophil recruitment, while murine models revealed a direct role in epidermal barrier dysfunction and chronic inflammation. Importantly, basophils exhibit context-dependent roles, also contributing to wound healing, highlighting the complexity of their function. In allergic asthma, they exacerbate responses by influencing memory Th2 cell migration, mucus production, and ILC2 activation. The long recognized epidemiological link between AD and allergic asthma underscores a critical gap in understanding how skin sensitization contributes to distal organ inflammation. Here, we discuss recent evidence establishing basophils as mediators of allergy, focusing on their role in sensitizing the lung via skin inflammation and exacerbating allergic lung disease. We highlight the mechanistic contribution of basophils to the comorbidity observed between skin and lung allergic diseases. Ultimately, understanding these mechanisms presents translational opportunities for therapeutic interventions aimed at preventing skin-mediated allergic sensitization and mitigating systemic allergic responses.