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    The International Society for Aerosols in Medicine

    Alexander Eggel

    Alexander Eggel

    Alexander Eggel

    University Hospital Bern  
    Bern, Switzerland

    After finishing my PhD in Immunology at the University of Bern under the supervision of Prof. em. Beda M. Stadler I completed a postdoctoral training at Stanford University in the group of Prof. Tony Wyss-Coray. Since 2013 I am an independent research group leader at the University of Bern from which I received the “Venia Docendi in Experimental Immunology” in 2017.

    Establishment of an allergic lung inflammation mouse model for pre-clinical testing of novel anti-human IgE drug candidates

    Abstract

    Upon inhalation of allergens, immunoglobulin E (IgE) sensitized airway mast cells degranulate and release soluble mediators promoting allergic symptoms. We have recently described a novel class of disruptive anti-IgE inhibitors, which not only suppresses IgE binding to its primary receptor FcεRI on mast cells but also actively removes FcεRI-bound IgE from allergic effector cells. While it is not feasible to study such novel anti-human IgE drug candidates in patients, pre-clinical in vivo model systems that recapitulate allergic manifestations in humans are of highest importance. Here, we describe the establishment of an allergic lung inflammation model using double transgenic mice expressing the human immunoglobulin epsilon heavy chain (huIgε) and the human FcεRI alpha-chain (huFcεRIα).

    Double transgenic huIgε/huFcεRIα+/+ mice were sensitized on atopic dermatitis-like skin lesions with the model antigen ovalbumin prior to intranasal antigen challenge. Allergic sensitization was associated with elevated total and allergen-specific serum IgE levels and infiltration of basophils, eosinophils and mast cells to the airways. In response to airway allergen challenge, increased expression of the mast cell specific protease Mcpt1 as well as the goblet cell specific mucin Muc5ac were observed in the airways of allergic mice.

    In summary, this huIgε/huFcεRIα+/+ double transgenic mouse model represents an interesting possibility for the pre-clinical in vivo testing of novel anti-human IgE drug candidates.

    1 Department for BioMedical Research, University of Bern, Switzerland
    2 Department of Rheumatology, Immunology and Allergology, University Hospital Bern, Switzerland
    3 Institute of Pathology, University of Bern, Switzerland