Vitamin D receptor upregulation in alloreactive human T cells

Joseph, Richard W.; Bayraktar, Ulas D.; Kim, Tae Kon; John, Lisa S. St.; Popat, Uday; Khalili, Jahan S.; Molldrem, Jeffrey J.; Wieder, Eric; Komanduri, Krishna V.

doi:10.1016/j.humimm.2012.04.019

Cited by 36 publications

(38 citation statements)

References 33 publications

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“…We noted that whereas 25(OH)D 3 at a physiological concentration of 100 nM induced maximum CD38 up-regulation, 1,25(OH) 2 D 3 was required at a 100-fold higher concentration (10 nM) than physiological levels (60–110 pM) to induce the same effect. That a supra-physiological concentration of 1,25(OH) 2 D 3 was required to obtain an effect in our study is in good line with previous studies [7,10-12,18,19]. However, in contrast to our observations that 25(OH)D 3 at 100 nM had a clear effect on T cells, most previous studies on 25(OH)D 3 required at least a 100-fold higher concentration of 25(OH)D 3 than found in serum to induce an effect [21].…”

Section: Resultssupporting

confidence: 93%

“…The serum concentration of the active 1,25(OH) 2 D 3 is approximately 1000-fold lower (60–110 pM) and far below the effective concentration of 1,25(OH) 2 D 3 found in in vitro studies. Thus, in most in vitro studies more than a 100-fold higher concentration of 1,25(OH) 2 D 3 than found in serum is often required to obtain an effect [7,10-12,18,19]. It has therefore been suggested that the level of circulating 1,25(OH) 2 D 3 is too low to affect immune responses in vivo , and that sufficient levels are obtained by local conversion of 25(OH)D 3 to 1,25(OH) 2 D 3 [20].…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D-binding protein controls T cell responses to vitamin D

et al. 2014

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BackgroundIn vitro studies have shown that the active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), can regulate differentiation of CD4+ T cells by inhibiting Th1 and Th17 cell differentiation and promoting Th2 and Treg cell differentiation. However, the serum concentration of 1,25(OH)2D3 is far below the effective concentration of 1,25(OH)2D3 found in in vitro studies, and it has been suggested that 1,25(OH)2D3 must be produced locally from the inactive precursor 25-hydroxyvitamin D3 (25(OH)D3) to affect ongoing immune responses in vivo. Although it has been reported that activated T cells express the 25(OH)D-1α-hydroxylase CYP27B1 that converts 25(OH)D3 to 1,25(OH)2D3, it is still controversial whether activated T cells have the capacity to produce sufficient amounts of 1,25(OH)2D3 to affect vitamin D-responsive genes. Furthermore, it is not known how the vitamin D-binding protein (DBP) found in high concentrations in serum affects T cell responses to 25(OH)D3.ResultsWe found that activated T cells express CYP27B1 and have the capacity to produce sufficient 1,25(OH)2D3 to affect vitamin D-responsive genes when cultured with physiological concentrations of 25(OH)D3 in serum-free medium. However, if the medium was supplemented with serum or purified DBP, DBP strictly inhibited the production of 1,25(OH)2D3 and 25(OH)D3-induced T cell responses. In contrast, DBP did not inhibit the effect of exogenous 1,25(OH)2D3. Actin, arachidonic acid and albumin did not affect the sequestration of 25(OH)D3 by DBP, whereas carbonylation of DBP did.ConclusionsActivated T cells express CYP27B1 and can convert 25(OH)D3 to 1,25(OH)2D3 in sufficiently high concentrations to affect vitamin D-responsive genes when cultured in serum-free medium. However, DBP sequesters 25(OH)D3 and inhibits the production of 1,25(OH)2D3 in T cells. To fully exploit the immune-regulatory potential of vitamin D, future studies of the mechanisms that enable the immune system to exploit 25(OH)D3 and convert it to 1,25(OH)2D3in vivo are required.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-014-0035-2) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Vitamin D-binding protein controls T cell responses to vitamin D

et al. 2014

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“…Vitamin D is intricately involved with T-cell proliferation and phenotype selection, which ultimately result in a reduction in the production of inflammatory cytokines. 24 In contrast to its effects in the adaptive immune system, the favorable effects of vitamin D in the innate immune response are mainly directed at macrophage activity. 25 Activated vitamin D stimulates differentiation of precursor monocytes to more mature phagocytic macrophages.…”

Section: Discussionmentioning

confidence: 99%

Deficiency in 25-Hydroxyvitamin D and 30-Day Mortality in Patients With Severe Sepsis and Septic Shock

Rech

Hunsaker

Rodriguez

2014

American Journal of Critical Care

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Background Vitamin D has immunomodulating properties. Objective To determine if vitamin D deficiency within 30 days of admission to the intensive care unit in patients with sepsis might be associated with increased all-cause 30-day mortality. Methods In a retrospective cohort study at a large, tertiary, urban, academic medical center, records of patients who had 25-hydroxyvitamin D levels measured within 30 days of admission for severe sepsis or septic shock from June 2006 to April 2011 were examined. Patients were considered deficient in vitamin D if its serum concentration was 15 ng/mL or less. The primary outcome of interest was 30-day mortality. Results Among the 121 patients in the sample, 65 (54%) were vitamin D deficient. Baseline demographics were similar between vitamin D deficient and nondeficient groups, except that the vitamin D deficient group had more African Americans (P = .01). All-cause 30-day mortality was significantly higher in patients deficient in vitamin D (37% vs 20%; P = .04) and remained higher at 90 days (51% vs 25%, P = .005). In multivariate analysis, age (odds ratio, 1.04; 95% CI 1.01–1.07; P = .01) and vitamin D deficiency (odds ratio, 2.7; 95% CI, 1.39–18.8; P = .02) were independently associated with increased 30-day mortality. Conclusion Patients deficient in vitamin D within 30 days of hospital admission for severe sepsis or septic shock may be at increased risk for all-cause 30-day mortality.

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“…Although the presence of the VDR have been described in the SN, there is no concrete evidence to describe the presence of this receptor in pigment cells or adrenergic cells and also no recorded evidence as to how they moderate cellular activities in the SN [11]. Other studies have shown that presence of corticosteroids like hydrocortisone did increase the gene transcription rate of VDR genes detected using RT-PCR; an act which is complementary in VDR up-regulation [12]. We are modeling the melanocytes in fish scale as the adrenergic neurons MT and pigment system [13,14].…”

Section: Introductionmentioning

confidence: 96%

VDR Potentiation and NMDA R Inhibition Facilitates Axo-Dendritic Process Formation in Melanocyte Model for Pigmented Cells in Parkinsonism

Michael

Ajonijebu²,

Chris³

et al. 2013

Cell Development Biol

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Background: A major cellular change in dopaminergic neurons leading to Parkinsonism is the alteration of microtubule proteins that causes accumulation of tau protein, α-syn and β-amyloid plaque in the cells. In this study we investigate the role of Vitamin D 3 in relieving the symptoms of Parkinsonism as it is capable of stimulating polymerization of microtubules. The Microtubules (MT) system in the fish scale melanocytes has been modeled for the dopaminergic neurons of the Substantia Nigra (SN). These cells are capable of forming cellular processes similar to what is seen in the dopaminergic neurons; in this study, we investigate the protective effect of Vitamin D 3 Receptor Agonist (VDRA) and N-Methyl-D-Aspartate Receptor (NMDA R) inhibition in process formation, synaptic denervation and melanin loss in fish scale melanocytes modeled as pigmented adrenergic cells.

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Vitamin D receptor upregulation in alloreactive human T cells

Cited by 36 publications

References 33 publications

Vitamin D-binding protein controls T cell responses to vitamin D

Vitamin D-binding protein controls T cell responses to vitamin D

Deficiency in 25-Hydroxyvitamin D and 30-Day Mortality in Patients With Severe Sepsis and Septic Shock

VDR Potentiation and NMDA R Inhibition Facilitates Axo-Dendritic Process Formation in Melanocyte Model for Pigmented Cells in Parkinsonism

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