Abstract
BackgroundAirborne allergens can induce an immunological chronic disease characterized by airway hyper responsiveness and inflammation, mediated by exaggerated Th2 immune response. Allergen-specific immunotherapy (AIT) is effective for treating this condition because it is able to modify its natural course by opposing the underlying pathogenic mechanisms and determining immune suppression, immune deviation and tolerance. The rational for the present study was to investigate the possibility of improving allergoid-based IT in terms of efficacy and safety. Recently, 1α,25-dihydroxyvitamin D3 (VD3), the active metabolite of vitamin D3, was described to be a potent inducer of T regulatory cells and to be a good adjuvant in AIT settings.MethodsWe investigated whether the co-administration of VD3 could potentiate the effect of AIT even when added to a low dose of chemically-modified monomeric allergoid of Der p 2 (d2-OID), in a Derp p 2 (d2)-sensitized BALB/c mice model. Control groups where treated with sham, VD3 alone or d2-OID only.ResultsThe d2-OID alone was not fully successful, as expected for a low dose. VD3 administration was associated with some valuable, although limited, changes in the immunological parameters in the lung. On the contrary, the VD3 adjuvated allergoid vaccine induced the most prominent reduction of airway eosinophilia and Th2 cytokines and concomitant increase of T regulatory cells and IL-10 in the lung and Der p 2-specific IgG2a in the serum.ConclusionsThe addition of VD3 to a conventional AIT protocol would allow the reduction of allergoid dose needed and therefore, the production costs. Moreover, beneficial immunomodulatory effects have been achieved by the oral administration which might favour the management of the therapy by the patients and their adherence, possibly enhancing the efficacy of the treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12948-016-0044-1) contains supplementary material, which is available to authorized users.
Highlights
Airborne allergens can induce an immunological chronic disease characterized by airway hyper responsiveness and inflammation, mediated by exaggerated T-helper cell type 2 (Th2) immune response
All treatments seem to produce a slight decrease in IL-13 level, but only the chemically-modified monomeric allergoid of Der p 2 (d2-OID) + vitamin D3 (VD3) treatment was associated with a significant modification (p < 0.01 vs sham and p < 0.05 vs d2-OID treatments) (Fig. 3b)
TNF-α significantly decreased for the all groups of mice, but the change reached the highest significance for the d2-OID + VD3 group (p < 0.01)
Summary
Airborne allergens can induce an immunological chronic disease characterized by airway hyper responsiveness and inflammation, mediated by exaggerated Th2 immune response. 1α,25-dihydroxyvitamin D3 (VD3), the active metabolite of vitamin D3, was described to be a potent inducer of T regulatory cells and to be a good adjuvant in AIT settings. One of the most reliable mechanisms explaining the desensitizing action of AIT (allergen immunotherapy) is based on its ability to induce tolerogenic dendritic cells (DC) characterized by an immature immunophenotype (iDC, DC0); these latter are crucial in favouring. The biologically active form of vitamin D3 (VD3) seems a good adjuvant for AIT as for its ability of modulating the innate and adaptive immune response [7,8,9] and inhibit DCs differentiation maintaining them in a persistent state of immaturity, through the down-regulation of co-stimulatory molecules and reduction of pro-inflammatory cytokines [10]; making them unable to activate alloreactive T cells [7]. VD3 is able to expand in vitro PBMC-derived human Tregs (Foxp3hi) obtained from atopic allergic subjects [13]
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