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Targeting the vitamin D receptor inhibits the B cell‐dependent allergic immune response
Author(s) -
Hartmann B.,
Heine G.,
Babina M.,
Steinmeyer A.,
Zügel U.,
Radbruch A.,
Worm M.
Publication year - 2011
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2010.02513.x
Subject(s) - calcitriol receptor , immunoglobulin e , immune system , calcitriol , agonist , immunology , receptor , medicine , endocrinology , vitamin d and neurology , antibody , chemistry , biology
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. 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.