Analysis of the modulation of allergic immune responses in an establihed humanized mouse model

• Applicant: Privatdozentin Dr. Iris Bellinghausen
• Subject Area: Dermatology
• Term: from 2010 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 174352829

Nowadays, more than 25% of the population in industrial countries are affected by immediate-type hypersensitivity reactions mediated by IgE (type I hypersensitivity according to Coombs and Gell) such as allergy rhinitis (hay fever), asthma and atopic eczema. Due to intensive research on basis of in vitro studies with human immune cells and different murine in vivo models of allergy fundamental mechanisms of allergic type I reactions have been elucidated within the last years. However, findings from human in vitro studies are restricted and the immune system of humans and mice differs in several aspects so that the transferability of experimental results from mice to men is limited. New models such as humanized mice are necessary to analyze the interaction of human immune cells under as far as possible physiological conditions particularly to test new therapeutic strategies. During the first period of this application a humanized mouse model of immediate-type allergy has been established by injection of human cells of allergic donors in immunodeficient mice resulting in the measurement of an allergen-specific gut and lung inflammation. The aim of the follow-up application is the analysis of novel therapeutic approaches in this model. That includes the immunomodulation by regulatory T cells and tolerogenic dendritic cells and the improvement of allergen-specific immunotherapy by combination of allergens and adjuvants such as CpG oligonucleotides, lipopeptides or lipopolysaccharides. This is of great interest particularly with regard to food allergy where therapeutic interventions are limited so far. Additionally, the employment of the humanized mouse model in relation to gut inflammation in celiac disease shall be analyzed.

• DFG Programme: Research Grants