Dust mite allergen-specific immunotherapy increases IL4 DNA methylation and induces Der p-specific T cell tolerance in children with allergic asthma.

Abstract

Allergen-specific immunotherapy (allergen-SIT) is a highly effective treatment for children with allergic asthma (AA), an immune-mediated chronic disease leading to bronchial muscle hypertrophy and airway obstruction in response to specific allergens. T helper cells and secreted cytokines play important roles in the pathogenesis of asthma, and epigenetic modulation controls genes important for T cell development and cytokine expression. This study evaluated T helper cell-secreted cytokines and DNA methylation patterns in children treated with Dermatophagoides pteronyssinus (Der p) allergen-SIT. Our results showed that after Der p challenge, peripheral blood mononuclear cells (PBMCs) from the SIT group, compared with the non-SIT AA group, produced lower levels of IL-4, IL-5 and IL-2. The SIT group, compared with the AA group, exhibited decreased sensitivity to the Der p allergen, concurrent with IL-4 down-modulation due to increased promoter DNA methylation, as estimated in PBMCs. Our results showed that SIT decreased IL-4 and IL-5, and inhibited T cell proliferation, by inhibiting IL-2 production after the specific allergen challenge. These results suggest that decreased IL-2 production and increased IL-4 cytokine promoter methylation is a potential mechanism of Der p-specific allergen desensitization immunotherapy.