Edited by: Hans-Uwe Simon
Targeting the vitamin D receptor inhibits the B cell-dependent allergic immune response
Article first published online: 1 DEC 2010
© 2010 John Wiley & Sons A/S
Volume 66, Issue 4, pages 540–548, April 2011
How to Cite
Hartmann, B., Heine, G., Babina, M., Steinmeyer, A., Zügel, U., Radbruch, A. and Worm, M. (2011), Targeting the vitamin D receptor inhibits the B cell-dependent allergic immune response. Allergy, 66: 540–548. doi: 10.1111/j.1398-9995.2010.02513.x
- Issue published online: 24 FEB 2011
- Article first published online: 1 DEC 2010
- Accepted for publication 28 October 2010
- B cells;
- immunoglobulin E;
- vitamin D;
- vitamin D receptor
To cite this article: Hartmann B, Heine G, Babina M, Steinmeyer A, Zügel U, Radbruch A, Worm M. Targeting the vitamin D receptor inhibits the B cell-dependent allergic immune response. Allergy 2011; 66: 540–548.
Background: 1α,25-dihydroxyvitamin D3 (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.