Intestinal IL-25 signal and ILC2 regulates the susceptibility to IgE-mediated experimental food allergy (MUC8P.813)

Abstract Food allergy is an IgE-mediated disorder manifested by uncontrolled type-2 immune response in the gastrointestinal tract. Little is known about the underlying mechanisms that drive the propensity to develop food-induced intestinal hypersensitivity. IL-25 is a distinct member of IL-17 inflammatory cytokine family, functioning at evoking type-2 inflammatory response. We aimed at investigating the involvements of IL-25 and its responding cells in the development of IgE-mediated experimental food allergy. We observed that IL-25 expression was rapidly elevated in the epithelium of inflamed duodenum before the onset of anaphylactic reaction to ingested allergens. Mice overexpressing intestinal IL-25 or deficient of IL-17RB displayed exacerbated or attenuated symptomatic features of IgE-mediated experimental food allergy, respectively. Subsequent analysis revealed that Lin-IL-17RB+ type-2 innate lymphoid cells (ILC2) that reside in the laminar propria of small intestine prior to the development of IgE-mediated experimental food allergy are the primary producers of Th2 cytokine, IL-5 and IL-13, in response to IL-25 stimulation. Furthermore, irradiated mice reconstituted with bone marrow cells that are deficient of RoRα or IL-17RB became resistant to developing IgE-mediated experimental food allergy. Our results suggest that intestinal ILC2 residents are poised to respond to induced IL-25 and function in promoting the development of IgE-mediated experimental food allergy.