IgE promotes type 2 innate lymphoid cells in murine food allergy

摘要

Summary Background Mast cells serve an important sentinel function at mucosal barriers and have been implicated as key early inducers of type 2 immune responses in food allergy. The generation of Th2 and IgE following food allergen ingestion is inhibited in the absence of mast cells. Group 2 innate lymphoid cells are also thought to play an important early role in nascent allergic responses. Objective To test whether IgE‐mediated mast cell activation promotes intestinal ILC 2 responses following ingestion of food allergens and whether ILC 2 amplify food allergy. Methods Two different mouse models of food allergy, one using intraperitoneally ovalbumin ( OVA )‐primed BALB /c animals and the other using enterally peanut‐sensitized inherently atopic IL 4raF709 mice, were applied to test the contributions of IgE antibodies and mast cells to ILC 2 responses. The effect of ILC 2 on mast cell activation and on anaphylaxis was tested. Results ILC 2 responses were significantly impaired in both models of food allergy in Igh7 ?/? mice harbouring a targeted deletion of the gene encoding IgE. A similar reduction in food allergen‐induced ILC 2 was observed in mast cell‐deficient Il4raF709 Kit W‐sh mice, and this was partially corrected by reconstituting these animals using cultured bone marrow mast cells. Mast cells activated ILC 2 for IL ‐13 production in an IL ‐4Rα?dependent manner. Activated ILC 2 amplified systemic anaphylaxis by increasing target tissue sensitivity to mast cell mediators. Conclusions and Clinical Relevance These findings support an important role for IgE‐activated mast cells in driving intestinal ILC 2 expansion in food allergy and reveal that ILC 2, in turn, can enhance responsiveness to the mediators of anaphylaxis produced by mast cells. Strategies designed to inhibit IgE signalling or mast cell activation are likely to inhibit both type 2 immunity and immediate hypersensitivity in food allergy.