title: 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.
authors.affiliation: Department of Dermatology, Venerology and Allergy, Allergy-Center-Charité, Charité Campus Mitte, Charité - Universitätsmedizin, D-10117 Berlin, Germany;
authors.forename: Guido
authors.initials: G
authors.lastname: Heine
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin, D-10117 Berlin, Germany;
authors.forename: Christoph
authors.initials: C
authors.lastname: Tabeling
authors.affiliation: Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305;
authors.forename: Bjoern
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin, D-10117 Berlin, Germany;
authors.forename: Carla R
authors.initials: CR
authors.lastname: González Calera
authors.affiliation: Department of Internal Medicine, Rheumatology and Clinical Immunology, Research Center Immuno Sciences, Charité Campus Benjamin Franklin, Charité - Universitätsmedizin, D-10117 Berlin, Germany; and.
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.affiliation: Department of Dermatology, Venerology and Allergy, Allergy-Center-Charité, Charité Campus Mitte, Charité - Universitätsmedizin, D-10117 Berlin, Germany;
authors.forename: Juliane
authors.initials: J
authors.lastname: Lindner
authors.affiliation: Deutsches Rheuma-Forschungszentrum Berlin, D-10117 Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin, D-10117 Berlin, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Witzenrath
authors.affiliation: Department of Dermatology, Venerology and Allergy, Allergy-Center-Charité, Charité Campus Mitte, Charité - Universitätsmedizin, D-10117 Berlin, Germany; margitta.worm@charite.de.
authors.forename: Margitta
authors.initials: M
authors.lastname: Worm
mesh_terms: D000818:Animals; D002112:Calcifediol / Q000008:administration & dosage* / Q000097:blood / Q000172:deficiency*; D003888:Desensitization, Immunologic / Q000379:methods; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004359:Drug Therapy, Combination; D005260:Female; D006967:Hypersensitivity / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000633:toxicity; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000276:immunology / Q000628:therapy; D013997:Time Factors
chemical_list: D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin; D002112:Calcifediol