Systemic IgE promotes allergic rhinitis by licensing Th2-to-Tfh conversion and local IgE production

mice, or in mice receiving OVA-Th2 cells deficient in IL-4-producing T follicular helper (Tfh) cell differentiation. Notably, when IgE-independent mast cell activation was induced by repeated intranasal administration of compound 48/80 in mice that had received OVA-Th2 cells, subsequent OVA challenge elicited OVA-specific AR symptoms and induced IgE-producing cells in the cLNs. Single-cell RNA sequencing revealed that systemic OVA-IgE facilitated the differentiation of OVA-Th2 cells into Tfh cells upon OVA challenge. Together, systemic IgE-mediated mast cell/basophil activation promoted Th2-to-Tfh differentiation and local IgE production, thereby contributing to the AR symptoms.