Dendritic cells as key targets for immunomodulation by Vitamin D receptor ligands

Adorini, Luciano; Penna, Giuseppe; Giarratana, Nadia; Roncari, Andrea; Amuchastegui, Susana; Daniël, Kenn C.; Uskoković, Milan R.

doi:10.1016/j.jsbmb.2004.03.013

Cited by 183 publications

(147 citation statements)

References 47 publications

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“…The shift appeared to be antigen specific and is probably caused by the direct interference of 1,25(OH) 2 D 3 or its analogues by the antigenpresenting dendritic cells. Indeed, 1,25(OH) 2 D 3 induces a reshaping of dendritic cells towards tolerogenic cells [69,70,77]. We have also demonstrated that dendritic cells generated in the presence of 1,25(OH) 2 D 3 or an analogue can re-direct already committed T cell clones derived from a type 1 diabetic patient towards non-proliferation [8,91].…”

Section: Vitamin D and Type 1 Diabetesmentioning

confidence: 57%

“…Whereas the renal enzyme is principally under the control of calcaemic and bone signals (such as para- [17]. A unique feature of 1,25(OH) 2 D 3 as an immunomodulator is that not only does it interact with T cells, but it also -more importantly-targets the central cell in the immune cascade, the antigen-presenting cell (for reviews see [69,70]) (Fig. 3).…”

Section: Vitamin D and Type 1 Diabetesmentioning

confidence: 99%

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Vitamin D and diabetes

et al. 2005

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Vitamin D deficiency predisposes individuals to type 1 and type 2 diabetes, and receptors for its activated form-1α,25-dihydroxyvitamin D 3 -have been identified in both beta cells and immune cells. Vitamin D deficiency has been shown to impair insulin synthesis and secretion in humans and in animal models of diabetes, suggesting a role in the development of type 2 diabetes. Furthermore, epidemiological studies suggest a link between vitamin D deficiency in early life and the later onset of type 1 diabetes. In some populations, type 1 diabetes is associated with certain polymorphisms within the vitamin D receptor gene. In studies in nonobese diabetic mice, pharmacological doses of 1α,25-dihydroxyvitamin D 3 , or its structural analogues, have been shown to delay the onset of diabetes, mainly through immune modulation. Vitamin D deficiency may, therefore, be involved in the pathogenesis of both forms of diabetes, and a better understanding of the mechanisms involved could lead to the development of preventive strategies.

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Section: Vitamin D and Type 1 Diabetesmentioning

confidence: 57%

Section: Vitamin D and Type 1 Diabetesmentioning

confidence: 99%

Vitamin D and diabetes

et al. 2005

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“…It is known that vitamin D has a wide range of biological actions (Table 2), [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] and that vitamin D receptor is present in most tissues and cells in the body. 26 As a result, it is not unexpected that multiple studies 27 have associated vitamin D deficiency with cardiovascular diseases, type 2 diabetes, hypertension, many types of cancer, rheumatoid arthritis, Crohn's disease, multiple sclerosis, asthma, and infectious diseases.…”

Section: Vitamin D and Extraskeletal Diseasesmentioning

confidence: 99%

“…Immune system Hypovitaminosis D inhibits maturation of monocyte-derived dendritic cells 20 Low 25(OH)D levels are associated with SLE 21 Oncological diseases 25(OH)D reduces aromatase expression reducing breast cancer growth 22 Low 25(OH)D is associated with high incidence of cancers of colon, 23 breast and prostate 24 High dosage (1000 IU/d) of vitamin D can reduce the risk for total cancer 25 BMD, bone mineral density; SLE, systemic lupus erythematosus. of type 2 diabetes mellitus, hypertension, hyperlipidemia, and peripheral vascular disease, coronary artery disease, myocardial infarction, heart failure, and stroke.…”

Section: Potential Role Of Vitamin D In Older Peoplementioning

confidence: 99%

“…Studies in vitro have shown that 1.25(OH)D seems to be able to inhibit maturation of monocyte-derived dendritic cells, impairing their ability to process and present antigen to T lymphocytes. 20 T lymphocyte expression of VDR increases upon antigenic activation and their activation determines a suppression of cell-mediated and promotion of humoral immune process. 42 On these basis 1.25(OH)D appears able to regular and probably to contain autoimmune pathological mechanisms.…”

Section: Immunomodulation Effectmentioning

confidence: 99%

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Potential role of vitamin D in prevention of skeletal and extraskeletal diseases in older people

Montagnani

Nardi²,

Cercignani

et al. 2015

Ital J Med

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Vitamin D and calcium are essential for bone health. An adequate calcium-phosphorus product determines a high quality mineralization long lifetime. In older people, both calcium and vitamin D levels may be lower causing osteomalacia and/or osteoporosis with a higher risk of fracture. Epidemiological data have clearly associated serum vitamin D lower levels (deficiency) with bone fracture in older people, however, not univocal data exist in regard to a beneficial effect of vitamin D supplementation in general population. Although not systematic, the present review aims to make a narrative synthesis of the most recent published data on vitamin D effect not only on bone, classical target associated with vitamin D studies, but namely on extraskeletal diseases. In fact, recently, there has been an increasing interest on this latter issue with surprising findings. Vitamin D, and in particular its deficiency, seems to have a role in pathophysiological pathways in several diseases involving cardiovascular, central nervous system and neoplastic process. On the other hand, vitamin D supplementation may modify the outcome of a wide range of illnesses. Up to date the data are conflicting mainly because of difficulty to establish a consensus on the threshold of vitamin D deficit. The US Institute of Medicine recommends to distinguish a level of insufficiency [defined as 30-50 nmol/L or 16-25 ng/mL of 25(OH)D] and another of deficiency identified by 25(OH)D levels lower than 30 nmol/L (or <16 ng/mL). This latter level is considered a minimum level necessary in older adults to minimize the risk of falls, fracture and probably to have some effects of vitamin D supplementation in extraskeletal diseases. Although there are no absolute certainties in such issue, the most recent data suggest that vitamin D deficiency, and its supplementation, may play an important role in a wide range of diseases other than in bone metabolic diseases in older but not in general population. For such reason a widespread measurement of vitamin D levels in general population, and not only in older, seems to be inappropriate and it could induce an overuse of vitamin D supplementation in situations in which its efficacy and cost-effectiveness have not been proven.

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The vitamin D receptor gene FokI polymorphism: Functional impact on the immune system

et al. 2007

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1a,25-Dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) has important effects on the growth and function of multiple cell types. These pleiotropic effects of 1,25(OH) 2 D 3 are mediated through binding to the vitamin D receptor (VDR). Several polymorphisms of the human VDR gene have been identified, with the FokI polymorphism resulting in VDR proteins with different structures, a long f-VDR or a shorter F-VDR. The aim of this study was to investigate the functional consequences of the FokI polymorphism in immune cells. In transfection experiments, the presence of the shorter F-VDR resulted in higher NF-jBand NFAT-driven transcription as well as higher IL-12p40 promoter-driven transcription. Marginal differences were observed for AP-1-driven transcription, and no differential effects were observed for transactivation of a classical vitamin D-responsive element. Concordantly, in human monocytes and dendritic cells with a homozygous short FF VDR genotype, expression of IL-12 (mRNA and protein) was higher than in cells with a long ff VDR genotype. Additionally, lymphocytes with a short FF VDR genotype proliferated more strongly in response to phytohemagglutinin. Together, these data provide the first evidence that the VDR FokI polymorphism affects immune cell behavior, with a more active immune system for the short F-VDR, thus possibly playing a role in immune-mediated diseases.

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Dendritic cells as key targets for immunomodulation by Vitamin D receptor ligands

Cited by 183 publications

References 47 publications

Vitamin D and diabetes

Vitamin D and diabetes

Potential role of vitamin D in prevention of skeletal and extraskeletal diseases in older people

The vitamin D receptor gene FokI polymorphism: Functional impact on the immune system

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