IL-4 receptor alpha blockade in mice reduces skin inflammation, systemic response and the atopic march

Abstract

AbstractAtopic dermatitis (AD) commonly precedes food allergy and asthma in the atopic march. Epicutaneous (EC) sensitization in mice with ovalbumin (OVA) results in allergic skin inflammation that mimics AD and promotes food anaphylaxis or asthma following a gastric or intranasal challenge with OVA, respectively. Using our mouse model of EC sensitization with OVA we evaluate whether anti-IL-4Rα blocking antibody improve allergic skin inflammation and impact the atopic march. IL-4Rα blockade at the end of EC sensitization decreased allergic skin inflammation in OVA-sensitized mice, evidenced by significantly decreased eosinophil infiltration, decrease production of IL-4, IL-13 by OVA- restimulated splenocytes and reduced serum levels OVA-specific IgE. However, late IL- 4Rα blockade did not affect food anaphylaxis or airway inflammation in EC sensitized mice following an oral or intranasal challenge with OVA. IL-4Rα blockade at the beginning of EC sensitization not only impact allergic skin inflammation and systemic response to the antigen, but also decreased food anaphylaxis or airway inflammation following OVA challenge. These results suggest that the blockade of sensitization through the skin by IL-4Rα blockade could impact the atopic march.