25-Hydroxvitamin D3 Promotes the Long-Term Effect of Specific Immunotherapy in a Murine Allergy Model

Abstract

Calcitriol (1α,25-dihydroxyvitamin D3) is the active vitamin D metabolite and mediates immunological functions, which are relevant in allergy. Its therapeutic use is limited by hypercalcaemic toxicity. We have previously shown that the activation of the vitamin D receptor inhibits IgE production and that B cells can synthesize calcitriol from its precursor 25-hydroxyvitamin D3 (inactive precursor) [25(OH)D] upon antigenic stimulation. In this study, we address the impact of 25(OH)D on the development of type I sensitization and determine its role in allergen-specific immunotherapy. BALB/c mice were sensitized to OVA, under 25(OH)D-deficient or sufficient conditions. The humoral immune response over time was measured by ELISA. OVA-specific immunotherapy was established and studied in a murine model of allergic airway inflammation using lung histology, pulmonary cytokine expression analysis, and functional parameters in isolated and perfused mouse lungs. In 25(OH)D-deficient mice, OVA-specific IgE and IgG1 serum concentrations were increased compared with control mice. OVA-specific immunotherapy reduced the humoral immune reaction after OVA recall dose-dependently. Coadministration of 25(OH)D in the context of OVA-specific immunotherapy reduced the allergic airway inflammation and responsiveness upon OVA challenge. These findings were paralleled by reduced Th2 cytokine expression in the lungs. In conclusion, 25(OH)D deficiency promotes the development of type I sensitization and correction of its serum concentrations enhances the benefit of specific immunotherapy.

Vitamin D and Serum Immunoglobulin E Levels in Allergic Rhinitis: A Case-control Study from Pakistan

“…In Heine et al, vitamin D supplementation in vitamin D deficient mice resulted in immunomodulation, which favored protection against allergic triggers. Production of pro-inflammatory cytokines was reduced and that of anti-inflammatory cytokines was increased by vitamin D supplementation [22]. Jerzynska et al supplemented children with vitamin D during the pollen season and observed fewer manifestations of AR as compared to the placebo group [23].…”

Laser-facilitated epicutaneous immunotherapy to IgE-mediated allergy

“…The effect of VD3 (calcipotriol) may be ascribed to its ability to induce immune tolerogenic dendritic cells and Treg cells [25,26]. In addition, it also inhibits activated antigen-specific T cell response and IgE expression in B-cells [26,27]. CpG as an adjuvant showed potential benefit to alleviate allergy symptoms by inducing T H 1 response [7,15,23].…”

Targeting the exposome: does correcting vitamin D deficiency have potential to treat and prevent asthma?

“…Vitamin D has been shown to promote multiple types of regulatory T cell including those expressing FoxP3 and those secreting interleukin-(IL-) 10, as well as enhancing expression of other immunomodulatory molecules such as CD200 and CD73, whilst suppressing effector T cells such as those of Th17 subtype [11,12]. Consistent with this, Heine and colleagues have in mice shown vitamin D deficiency to increase specific Immunoglobulin E (IgE) responses in an allergen sensitization model, with vitamin D supplementation enhancing allergen immunotherapy [13].…”