Targeting the vitamin D receptor inhibits the B cell-dependent allergic immune response.

Abstract

BACKGROUND:

1α,25-dihydroxyvitamin D(3) (calcitriol), the biologically active form of vitamin D, is an immunomodulatory hormone, e.g. it inhibits IgE synthesis in B cells. As its clinical application is limited by hypercalcemia, synthetic vitamin D receptor (VDR) agonists that mediate immunomodulatory activities without adverse hypercalcemic effects are of great interest. This study aimed to investigate the impact of a low-calcemic VDR agonist on the IgE immune response in vitro and in vivo.

METHODS:

Human peripheral B cells were cultured under IgE inducing conditions in the presence of VDR ligands. B cells were analyzed by quantitative RT-PCR, enzyme-linked immunosorbent assays, enzyme-linked immunospot technique, and flow cytometry. BALB/c mice were sensitized with ovalbumin (OVA)/alum followed by the therapeutic VDR agonist treatment and analyzed regarding the humoral immunoglobulin profile.

RESULTS:

The natural VDR ligand calcitriol, but also a low-calcemic VDR agonist, profoundly suppressed IgE production by human peripheral B cells by 63.9 ± 5.9%. The potential mechanisms involved are the reduction of the transcript for activation-induced deaminase (AID) and the reduction of IgE immunoglobulin-secreting cells by 68.1 ± 12.7%. By using an in vivo approach, we finally demonstrate that the humoral IgE response in a type I allergy mouse model was impaired by the VDR agonist.

CONCLUSION:

Our results show that targeting the VDR modulates the humoral immune response including IgE. Whether it might be useful for clinical applications has to be determined in appropriate clinical trials.

• Authors: B Hartmann, G Heine, M Babina, A Steinmeyer, U Zügel, A Radbruch, M Worm
• Journal: Allergy (Allergy) Vol. 66 Issue 4 Pg. 540-8 (Apr 2011) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 21121929 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 John Wiley & Sons A/S.

Chemical References

• Receptors, Calcitriol
• Vitamins
• Immunoglobulin E
• Calcitriol

Topics

• Animals
• B-Lymphocytes (drug effects, immunology)
• Calcitriol (pharmacology)
• Cell Separation
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Humans
• Hypersensitivity (immunology)
• Immunoglobulin E (biosynthesis, immunology)
• Mice
• Mice, Inbred BALB C
• Receptors, Calcitriol (immunology, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Vitamins (pharmacology)