Immune-gut interactions in food allergy and oral tolerance

Food allergy affects 8% of children and 10% of adults currently yet despite the increasing prevalence and severity, there is no curative treatment for food allergy 1. The paradigm-shifting LEAP study demonstrated that early oral introduction of peanut in the diet can prevent the development of peanut allergy 2. However, the mechanisms of oral tolerance in the gut underlying this effect are largely unknown.

Innate lymphoid cells (ILC) are likely to be the primary responders on the first exposure to food allergens in the gut and may drive the consequent response by the adaptive immune system leading to food allergy or oral tolerance3. Studies in mouse models demonstrated the involvement of ILC2 in the development of follicular helper cells and IgE sensitization and their ability to produce IL-4 and other Th2 cytokines and to suppress regulatory T cells leading to food allergy 4,5. These mouse studies need validation in human models and the mechanisms of oral tolerance development and of suppression of pathologic allergic responses deserve further research.

ILC can be divided into different subsets, with unique characteristics and functions, which are plastic and amenable to manipulation through control of their cytokine milleu. Thus, we aim to understand the role of each subset in food allergy to potentially develop new therapeutic approaches that would promote differentiation/plasticity towards protective ILC phenotypes. This could be achieved, for example, using monoclonal antibodies to target specific cytokine pathways and could lead to a much-needed cure for food allergy.

The Neves lab has previously established an in vitro system of human induced pluripotent stem cells derived intestinal organoids co-cultured with human ILC 6. Using this model we will study the involvement of ILCs in the primary response to food allergens in the gut and their interactions with epithelial cells and the adaptive immune system that lead to the development of food allergy or the establishment of oral tolerance to food allergens.