Effect of mite allergen immunotherapy on the altered phenotype of dendritic cells in allergic asthmatic children

Abstract

BackgroundAllergic asthma is a TH2 inflammatory disease. Dendritic cells (DCs) play key roles in the TH1/TH2 balance. Allergen specific immunotherapy (SIT) has the potential to modify the course of allergy because the ratio of TH1 to TH2 cytokines produced is increased after SIT. ObjectiveTo determine how SIT affects DCs in children and to define novel parameters of this treatment. MethodsWe investigated the changes of phenotypic and functional variations of monocyte-derived DCs from allergic asthmatic children undergoing complete mite SIT. Peripheral blood monocytes from SIT allergic asthmatic children, allergic asthmatic controls, and healthy controls were cultured with granulocyte-macrophage colony-stimulating factor and interleukin 4 and then stimulated with Dermatophagoides pteronyssinus (Der p) allergen or lipopolysaccharide (LPS). The expressions of surface molecules on monocyte-derived DCs were assessed by flow cytometry. Cytokine production by cultured monocyte-derived DCs was determined by enzyme-linked immunosorbent assay. ResultsAfter LPS stimulation, monocyte-derived DCs of the allergic asthmatic group had a higher CD86 and lower HLA-DR expression than the healthy controls. In SIT patients, the expression was similar to that of the healthy controls. After Der p stimulation monocyte-derived DCs of the allergic asthmatic patients displayed lower Toll-like receptor 4 (TLR4), whereas again in SIT patients the expression was similar to that of healthy controls. ConclusionThese findings indicate that SIT normalizes the expression of CD86, HLA-DR, and TLR4 on DCs. Moreover, CD86, HLA-DR, and TLR4 may be useful parameters for monitoring SIT. Decreased TLR4 expression in allergic asthmatic patients might be compensated by TLR4 agonists, with the potential of amplifying the effects of SIT.