Αρχειοθήκη ιστολογίου

Σάββατο 16 Δεκεμβρίου 2017

IgE promotes type 2 innate lymphoid cells in murine food allergy

Abstract

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 ILC2 responses following ingestion of food allergens and whether ILC2 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 IL4raF709 mice, were applied to test the contributions of IgE antibodies and mast cells to ILC2 responses. The effect of ILC2 on mast cell activation and on anaphylaxis was tested.

Results

ILC2 responses were significantly impaired in both models of food allergy in Igh7-/- mice harboring a targeted deletion of the gene encoding IgE. A similar reduction in food allergen-induced ILC2 was observed in mast cell deficient Il4raF709 KitW-sh mice and this was partially corrected by reconstituting these animals using cultured bone marrow mast cells. Mast cells activated ILC2 for IL-13 production in an IL-4Rα-dependent manner. Activated ILC2 amplified systemic anaphylaxis by increasing target tissue sensitivity to mast cell mediators.

Conclusions & clinical relevance

These findings support an important role for IgE-activated mast cells in driving intestinal ILC2 expansion in food allergy and reveal that ILC2, in turn, can enhance responsiveness to the mediators of anaphylaxis produced by mast cells. Strategies designed to inhibit IgE signaling or mast cell activation are likely to inhibit both Type 2 immunity and immediate hypersensitivity in food allergy.

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from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2k5E6fQ

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