As well as inducing the Th2/TFH2/TFH13 axis, the severity of IgE-mediated allergies has been associated with functional impairment of non-follicular [Treg (CXR5-FoxP3+IL-10+) and Tr-1 (CXCR5-FoxP3-IL-10+)] and follicular [TFR (CXCR5+ FoxP3+IL-10+)] regulatory CD4+ T cells (21, 22). This evidence concerns the gene IGHE and allergic disease.