These findings suggest that allergen-specific IgG antibodies can act to induce and sustain immunologic tolerance to foods.

Background Food allergy is a growing health problem with very limited treatment options. Investigation of the immunological pathways underlying allergic sensitization to foods in humans has been greatly constrained by the limited availability of intestinal tissue and gut-resident immune cells. While mouse models have offered insights into pathways of food sensitization, differences between rodent and human immune physiology limit the extension of these findings to our understanding of human disease. Objective To develop a strategy for the generation of mice with humanized adaptive immune systems, complete with tissue engraftment by human mast cells that are competent to mount specific IgE-mediated responses and drive systemic anaphylaxis upon ingestion challenge. Methods Non-obese diabetic (NOD) severe combined immunodeficient (SCID) mice lacking the cytokine receptor common gamma chain (γc−/−) and carrying a human stem cell factor (SCF) transgene were engrafted with human hematopoietic stem cells (HSC). The impact of peanut (PN) feeding and IgE neutralization on the development of immune responses, mast cell homeostasis and anaphylactic food allergy was assessed in these animals. Results NSG SCF (huNSG) mice exhibited robust engraftment with functional human T and B lymphocytes and human mast cells were found in significant numbers in their tissues, including the intestinal mucosa. Following gavage feeding with PN they mounted specific antibody responses, including PN-specific IgE. When enterally challenged with PN, they exhibited mast cell mediated systemic anaphylaxis, as indicated by hypothermia and increases in plasma tryptase levels. Anti-IgE (omalizumab) treatment ablated this anaphylactic response. Conclusions huNSG mice provide a novel tool for studying food allergy and IgE-mediated anaphylaxis.

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 signalling or mast cell activation are likely to inhibit both type 2 immunity and immediate hypersensitivity in food allergy.