Vitamin D receptor binds to the ε germline gene promoter and exhibits transrepressive activity

Milovanović, M; Heine, Guido; Hallatschek, Werner; Opitz, Bastian; Radbruch, Andreas; Worm, Margitta

doi:10.1016/j.jaci.2010.08.020

Cited by 40 publications

(37 citation statements)

References 34 publications

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“…These data are in line with previous data from mice treated with a synthetic low-calcaemic calcitriol-derivative (5) or vdr knockout mice (33). As 25(OH)D alone the absence of Ag is inactive in the concentrations determined, the reduced Ig response in the presence of 25(OH)D following Ag challenge supports the hypothesis that endogenous calcitriol signaling is dependent on CYP27B1 expression in activated immune cells, which leads to reduced IgE expression, as we have shown in human B cells (3,4). In 25(OH)Ddeficient mice, the OVA-specific serum IgE and IgG1 concentrations were comparable before the final OVA recall between sensitized mice without SIT, following SIT or D-SIT.…”

Section: Discussionsupporting

confidence: 64%

“…However, the long-term therapeutic use of calcitriol is limited by hypercalcemic side effects. We and others demonstrated that activated B lymphocytes (4), T cells (7), and myeloid APCs (8,9) can synthesize biologically active calcitriol from 25-hydroxyvitamin D 3 (10). Cord blood 25(OH)D levels were correlated with IL-10 levels and inversely with total IgE titers (11).…”

mentioning

confidence: 95%

“…We have previously shown that vitamin D receptor activation inhibits IgE expression in B cells (2) via recruitment of a VDR-DNA complex to the ε-switch transcript promoter (3). Furthermore, VDR activation enhances IL-10 expression in B cells after binding to its promoter (4).…”

mentioning

confidence: 99%

“…T he active metabolite of vitamin D termed calcitriol (1a,25-dihydroxyvitamin D 3 ) mediates anti-inflammatory functions after binding to the vitamin D receptor (VDR), which then acts as a transcription factor regulating specific target gene expression (1). We have previously shown that vitamin D receptor activation inhibits IgE expression in B cells (2) via recruitment of a VDR-DNA complex to the ε-switch transcript promoter (3).…”

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confidence: 99%

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

Heine

Tabeling

Hartmann

et al. 2014

The Journal of Immunology

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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.

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Section: Discussionsupporting

confidence: 64%

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confidence: 95%

mentioning

confidence: 99%

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confidence: 99%

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

Heine

Tabeling

Hartmann

et al. 2014

The Journal of Immunology

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“…Recent studies have demonstrated associations between vitamin D receptor polymorphism and asthma risk [76]; between genetic variants in the vitamin D activation enzyme, vitamin D levels, and total IgE [77]; and between low vitamin D intake during pregnancy and higher cord blood interleukin-10 levels [78], known to suppress IgE production (reviewed in [74]). Furthermore, vitamin D receptor agonists have been shown to suppress allergen-specific IgE synthesis in vitro and in vivo [79,80], modulate dendritic cell maturation to induce tolerogenic dendritic cells, induce regulatory CD4 + CD25 + forkhead box P3 (FoxP3) + T cells, but also FoxP3 -Treg1 cells expressing interleukin-10 [81••], thus affecting both T-helper type 1 (Th1) and Th2 cell function, as recently reviewed [74].…”

Section: Vitamin D and Immune Functionmentioning

confidence: 99%

Latitude, Sunlight, Vitamin D, and Childhood Food Allergy/Anaphylaxis

Mullins

Camargo

2011

Curr Allergy Asthma Rep

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Vitamin D is widely known for its role in bone metabolism, but this sterol hormone also has important immunomodulatory properties. Vitamin D is produced by the conversion of D3 in the skin following UVB exposure, or after ingestion of D2 or D3. At the extremes of latitude, there is insufficient UVB intensity in the autumn and winter months for adequate synthesis of vitamin D to occur. Growing evidence implicates vitamin D deficiency in early life in the pathogenesis of nonskeletal disorders (e. g., type 1 diabetes and multiple sclerosis) and, more recently, atopic disorders. Several studies have reported higher rates of food allergy/anaphylaxis or proxy measures at higher absolute latitudes. Although causality remains to be determined, these studies suggest a possible role for sunlight and/or vitamin D in the pathogenesis of food allergy/anaphylaxis.

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9‐cis Retinoic acid and 1.25‐dihydroxyvitamin D₃ drive differentiation into IgA⁺ secreting plasmablasts in human naïve B cells

et al. 2020

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Calcitriol and 9‐cis retinoic acid (9cRA) play a fundamental role in shaping the adaptive immune response by altering the Ig profile and the differentiation of B cells, controlled by their corresponding nuclear receptors, VDR and RAR. Herein, after the establishment of a plasmablast differentiation culture, we investigated how both ligands modulate human naïve B cell differentiation and to which extent VDR/RXR and RAR/RXR signaling interferes. Calcitriol and 9cRA mediated activation of purified naïve B cells resulted in a strong differentiation of CD27+ CD38+ plasmablasts and antibody secretion. The significant IgA response was preceded by a strong induction of α‐germline transcription (GLT). Induction of αGLT and consecutively IgA secretion driven by calcitriol is a novel observation and we show by magnetic chromatin IP that this was mediated by recruitment of the VDR to the TGF‐β promoter thus inducing TGF‐β expression. Finally, as revealed by transcriptomic profiling calcitriol and 9cRA modulate several signals required for differentiation and isotype switching in a noncompeting but rather additive manner. Calcitriol and 9cRA participate in the control of the IgA response in human activated naïve B cells. The balance between both ligands may be an important factor in channeling humoral immune responses toward a protective direction.

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Vitamin D receptor binds to the ε germline gene promoter and exhibits transrepressive activity

Cited by 40 publications

References 34 publications

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

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

Latitude, Sunlight, Vitamin D, and Childhood Food Allergy/Anaphylaxis

9‐cis Retinoic acid and 1.25‐dihydroxyvitamin D₃ drive differentiation into IgA⁺ secreting plasmablasts in human naïve B cells

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Vitamin D receptor binds to the ε germline gene promoter and exhibits transrepressive activity

Cited by 40 publications

References 34 publications

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

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

Latitude, Sunlight, Vitamin D, and Childhood Food Allergy/Anaphylaxis

9‐cis Retinoic acid and 1.25‐dihydroxyvitamin D3 drive differentiation into IgA+ secreting plasmablasts in human naïve B cells

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Product

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9‐cis Retinoic acid and 1.25‐dihydroxyvitamin D₃ drive differentiation into IgA⁺ secreting plasmablasts in human naïve B cells