Eosinophils as immunoregulatory players in allergic rhinitis: beyond cytotoxicity

Eosinophils have traditionally been viewed as terminal effector cells in allergic rhinitis (AR), driving tissue damage through the release of cytotoxic granule proteins and pro-inflammatory mediators. However, accumulating evidence over the past two decades has challenged this paradigm, revealing that eosinophils harbor a substantial immunoregulatory repertoire. This Mini Review synthesizes emerging findings on four underappreciated dimensions of eosinophil immunoregulatory function in the context of AR: (i) the capacity of eosinophils to produce interleukin-10 (IL-10) and engage in functional crosstalk with Foxp3+ regulatory T cells (Tregs); (ii) the dual role of eosinophil-derived transforming growth factor-beta (TGF-β) in both tissue remodeling and mucosal tolerance; (iii) eosinophil lipid mediator class-switching from pro-inflammatory cysteinyl leukotrienes (CysLTs) to specialized pro-resolving mediators (SPMs); and (iv) the functional heterogeneity between tissue-resident and inflammatory eosinophil subsets. We further discuss the clinical implications of these findings, including the paradoxical outcomes of anti-IL-5 therapies in AR and the potential of immunoregulatory eosinophil markers as biomarkers for allergen-specific immunotherapy (AIT). A deeper understanding of the context-dependent immunoregulatory functions of eosinophils in the nasal mucosa may inform precision therapeutic strategies that selectively target pro-inflammatory eosinophil subsets while preserving their homeostatic and tolerogenic roles.