Cartoon showing the complex regulatory activity of basophils following AIT. A) Initially, allergen challenge elicits a mast cell response, which triggers the type2 innate lymphoid cells (IL2Cs), via mediators such as LTD4 and PGD2, to support a type 2 immune response, with the production of IL4, IL5, IL13. B) Tissue allergen challenge induces the production of alarmins and cytokines, such as IL25 and IL33, which induce IL2Cs to the Th2 response and activate basophils to produce IL4, which in turn inhibit the activity of IL2Cs, to reduce (C) the onset of inflammation; D) In these circumstances, IL4 from basophils induces the differentiation and activation of Tregs, which in turn dampen allergy reactions (E) through cytokines (IL10, TGF-β) and IgG4; F) here basophils produce also IL9, which helps the differentiation of Tregs from naiveCD4+ T cells; G) the promotion of the development of IL17-producing T regs (Th17) from basophils contributes both in increasing IL9 and inhibiting CD4+CD25+Foxp3+ T regs differentiation, in order to switch off the Treg-mediated signaling. Green circle: activation (+), red circles inhibition (−).