1,25‐dihydroxyvitamin D<sub>3</sub> promotes IL‐10 production in human B cells

Heine, Guido; Niesner, Uwe; Chang, Hyun‐Dong; Steinmeyer, Andreas; Zügel, Ulrich; Zuberbier, Torsten; Radbruch, Andreas; Worm, Margitta

doi:10.1002/eji.200838216

Cited by 292 publications

(263 citation statements)

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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: 54%

“…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). Accordingly, we determined that allergen-specific IgE was diminished upon VDR activation in mice (5).…”

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confidence: 88%

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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: 54%

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confidence: 88%

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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“…The presence of VDRs in human T lymphocytes [Provvedini et al 1983;Baeke et al 2010], in greater number in CD8 than in CD4 lymphocytes [Vedman et al 2000], as well as in B lymphocytes [Provvedini et al 1983;Chen et al 2007], and the expression of CYP27B1 in lymph nodes [Zehdner et al 2001] and T lymphocytes [Sigmundsdottir et al 2007] constitute important indications of a potential role of vitamin D in adaptive immunity. Furthermore, a number of mechanisms by which vitamin D and calcitriol could favourably influence immunity have been reported in the past 30 years: it has been shown that vitamin D (through calcitriol) reduces differentiation of monocytes to DCs and differentiation and proliferation of DCs, thus decreasing T-cell stimulation [Griffin et al 2001]; controls T-cell activation [von Essen et al 2010] and inhibits T-cell proliferation [Rigby et al 1990;Lemire et al 1984]; reduces the production of interleukin (IL)-2 (growth factor for T cells) [Müller et al 1993]; suppresses in vitro and in vivo production of proinflammatory Th1 cell-derived IFNγ and tumour necrosis factor α [Reichel et al 1987;Lemire et al 1995;Baeke et al 2010;Zhang et al 2012]; reduces proinflammatory Th17 activity and IL-17 production [Tang et al 2009;Ikeda et al 2010;Bruce et al 2011;Joshi et al 2011;Allen et al 2012]; enhances the production of the antiinflammatory cytokine IL-10 [ Heine et al 2008;Baeke et al 2010;Allen et al 2012]; promotes in vitro and in vivo the development of Tregs expressing cytotoxic T lymphocyte antigen 4 and forkhead box P3, resulting in an anti-inflammatory effect [Jeffery et al 2009;Prietl et al 2010;Khoo et al 2012;Urry et al 2012]; enhances the transformation of CD4 T lymphocytes into a Th2 phenotype (with a protective role) [Boonstra et al 2001;…”

Section: General Immunodulatory Effect Of Vitamin D In Humansmentioning

confidence: 99%

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Pierrot‐Deseilligny

Souberbielle

2013

Ther Adv Neurol Disord

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Abstract:The contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis (MS) is reviewed. Among the multiple recently discovered actions of vitamin D, an immunomodulatory role has been documented in experimental autoimmune encephalomyelitis and in humans. This action in the peripheral immune system is currently the main known mechanism through which vitamin D might influence MS, but other types of actions could be involved within the central nervous system. Furthermore, vitamin D insufficiency is widespread in temperate countries and in patients with MS at the earliest stages of the disease, suggesting that the deleterious effects related to vitamin D insufficiency may be exerted in these patients. In fact, many genetic and environmental risk factors appear to interact and contribute to MS. In genetics, several human leukocyte antigen (HLA) alleles (more particularly HLA-DRB1*1501) could favour the disease whereas some others could be protective. Some of the genes involved in vitamin D metabolism (e.g. CYP27B1) also play a significant role. Furthermore, three environmental risk factors have been identified: past Epstein-Barr virus infection, vitamin D insufficiency and cigarette smoking. Interactions between genetic and environmental risk or protective factors may occur during the mother's pregnancy and could continue during childhood and adolescence and until the disease is triggered in adulthood, therefore possibly modulating the MS risk throughout the first decades of life. Furthermore, some clinical findings already strongly suggest that vitamin D status influences the relapse rate and radiological lesions in patients with MS, although the results of adequately powered randomized clinical trials using vitamin D supplementation have not yet been reported. While awaiting these incontrovertible results, which might be long in coming, patients with MS who are currently in vitamin D insufficiency should be supplemented, at least for their general health status, using moderate doses of the vitamin.

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“…Direct modulation of immune cells by vitamin D is most likely, as different immune cell types can produce and perceive calcitriol including monocytes, dendritic cells, T-helper cells and activated B cells (Hayes et al, 2003;Adorini and Penna, 2008). Previously, we demonstrated that activated human B cells can synthesize calcitriol from its precursor, which mediates enhanced expression of interleukin-10 (IL-10; Heine et al, 2008) and inhibited immunoglobulin E (IgE) production (Heine et al, 2002). In newborns, cord blood levels of 25-hydroxyvitamin D and the ratio of IL-10 to IgE are both higher in infants born in summer compared with winter (Zittermann et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Efficient tetanus toxoid immunization on vitamin D supplementation

et al. 2011

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Background/Objectives: Vitamin D mediates immunomodulatory functions, and its deficiency has been associated with an increased prevalence of immunological diseases. The supplementation of vitamin D might be therapeutically beneficial, for example, in lupus erythematosus patients. However, its affect on established recall immune responses is undefined. Subjects/Methods: In all, 32 individuals were randomized in a placebo controlled, double-blind setting, and received vitamin D (daily 2000 IU) for 10 weeks followed by tetanus toxoid (TT) booster immunization. Results: During vitamin D supplementation the median 25-hydroxyvitamin D serum concentration increased to 80.3 nM, which as expected decreased in the placebo group to 29.1 nM during the ultraviolet-deprived winter months. The TT-specific immunoglobulin G (IgG) boost efficiency was marginal higher in the vitamin D group (P ¼ 0.04). The increase of the 25-hydroxyvitamin D levels correlated with the increase of TT-IgG serum concentrations. The induction of specific serum IgA and specific antibody secreting cells was comparable between both groups. Accordingly, the TT-specific and polyclonally triggered T-cell cytokine profiles were stable as well. Conclusions: Vitamin D supplementation was successful and booster immunization induced efficiently specific antibodies titers.

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1,25‐dihydroxyvitamin D₃ promotes IL‐10 production in human B cells

Cited by 292 publications

References 49 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

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Efficient tetanus toxoid immunization on vitamin D supplementation

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1,25‐dihydroxyvitamin D3 promotes IL‐10 production in human B cells

Cited by 292 publications

References 49 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

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Efficient tetanus toxoid immunization on vitamin D supplementation

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Resources

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1,25‐dihydroxyvitamin D₃ promotes IL‐10 production in human B cells