Understand mechanisms of mast cell reactivity and induced anergy and how these are modulated by biologics in food allergy treatment

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Allergic diseases, such as asthma, allergic rhinitis, and food allergy, are an important public health burden and seriously affect the quality of life of people, particularly in developed countries. These conditions are characterized by the presence of IgE antibodies to common things in our environment, such as house dust mite (asthma), pollen (allergic rhinitis), and peanut (food allergy). The routes of allergens intake and the frequency are highly variable. For example grass pollen exposure is seasonal while food allergens are taken up accidentally and through the gastrointestinal tract. The symptoms associated with the latter are more systemic and severe compare to the inhalant allergen. Mast cells, together with basophils, are the main effector cells in IgE-mediated allergic reactions. During the allergic response, mast cells upon allergen encounter are activated and subsequently release rapidly their granular content, including histamine, cytokines, chemokines, proteases, and lipid mediators.Furthermore, the cytokine IL-33, produced by damaged epithelial cells contributes to acute allergic reactions by enhancing the IgE-mediated activation of mast cells. For patients allergic to multiple allergens, knowing which allergen or combinations of allergens are driving the symptoms is clinically relevant and as of yet is a poorly understood area. Furthermore, it remains unclear how allergen re-exposure, as well as combinations of unrelated allergens, affect mast cell activities. In addition, it is unclear what is the effect of treatment with biologics on mast cell responsiveness Therefore, the goal of the project is to gain a better understanding of the role of human mast cells in complex multi-allergen dominated allergic responses and investigate mechanisms of mast cell unresponsiveness. This project involves culturing and differentiation of human mast cells and the evaluation of their function by flow cytometry (e.g. CyTOF), advanced immunofluorescence, transcriptomic analysis and bioinformatics analysis. Moreover, this project will be combining mast cell-centred immunology research and allergy clinical expertise at the internationally recognised Manchester Collaborative Centre of Inflammation Research and Lydia Becker Institute of Immunology and Inflammation.