1,25-Dihydroxyvitamin D3 Selectively Modulates Tolerogenic Properties in Myeloid but Not Plasmacytoid Dendritic Cells

Penna, Giuseppe; Amuchastegui, Susana; Giarratana, Nadia; Daniël, Kenn C.; Vulcano, Marisa; Sozzani, Silvano; Adorini, Luciano

doi:10.4049/jimmunol.178.1.145

Cited by 315 publications

(255 citation statements)

References 64 publications

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“…42 The role of vitamin D as a coordinator of other T lymphocyte phenotypes such as IL-17-secreting T lymphocytes (T H 17 lymphocytes) has yet to been fully elucidated, but it is interesting to note that when nonobese diabetic (NOD) mice (a strain susceptible to auto immune disease) were treated with an analog of 1,25(OH) 2 D, they showed decreased expression of IL-17. 43 In addition to proliferation and differentiation, a key component of T lymphocyte adaptive immunity is the manner in which lymphocytes 'home' to particular tissues and are retained or removed from these sites.…”

Section: Vitamin D Antigen Presentation and Adaptive Immunitymentioning

confidence: 99%

Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity

2008

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SUMMARYKnowledge about the ability of vitamin D to function outside its established role in skeletal homeostasis is not a new phenomenon. Nonclassical immunomodulatory and antiproliferative responses triggered by active 1,25-dihydroxyvitamin D were first reported more than a quarter of a century ago. It is only in recent years, however, that there has been a significant improvement in our understanding of how these nonclassical effects of vitamin D can influence the pathophysiology and possible prevention of human disease. Three particular strands of evidence have been prominent: firstly, population studies have revised our interpretation of normal vitamin D status in humans, suggesting, in turn, that vitamin D insufficiency is a clinical problem of global proportions; secondly, epidemiology has linked vitamin D status with disease susceptibility and/or mortality; and, thirdly, expression of the machinery required to synthesize 1,25-dihydroxyvitamin D in normal human tissue seems to be much more widespread than originally thought. Collectively, these observations suggest that nonclassical metabolism and response to vitamin D might have a significant role in human physiology beyond skeletal and calcium homeostasis. Specific examples of this will be detailed in the current Review, with particular emphasis on the immunomodulatory properties of vitamin D.

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Section: Vitamin D Antigen Presentation and Adaptive Immunitymentioning

confidence: 99%

Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity

2008

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“…In this context, PDCs have also been implicated in autoimmune diseases by promoting Th17 immune responses through the production of IL1b and IL23p19 [88,89]. Moreover, by secreting CCL4, PDCs might be involved in regulatory T cell recruitment to the tumor site, representing an additional mechanism for controlling immune function [90].…”

Section: Reviewmentioning

confidence: 99%

Trafficking properties of plasmacytoid dendritic cells in health and disease

Sozzani

Vermi

Prete

et al. 2010

Trends in Immunology

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“…It also suppresses T cell proliferation and differentiation [10]. 1,25(OH) 2 D 3 is known to induce a more tolerogenic phenotype in dendritic cells [11]. In addition, it can skew T cell response toward a T helper (Th) 2 profile [7,12].…”

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confidence: 99%

1,25-dihydroxyvitamin D3 Modulates Cytokine Production Induced by Candida albicans: Impact of Seasonal Variation of Immune Responses

Khoo

Chai

Koenen

et al. 2011

The Journal of Infectious Diseases

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Background. Our interest in immunological effects produced by vitamin D 3 (1,25(OH) 2 D 3 ) and its therapeutic potential prompted us to examine the role of 1,25(OH) 2 D 3 on cytokine production by Candida albicans.Methods. Peripheral blood mononuclear cells (PBMC) with stimulated C. albicans and 1,25(OH) 2 D 3 , cytokine concentrations were measured in supernatant. Quantitative polymerase chain reaction (qPCR) was performed for T cell transcription factors, SOCS1 and 3. TLR2/4, Dectin-1, and mannose receptor expression was studied using flow cytometry and qPCR. An ex-vivo stimulation study was carried out in healthy volunteers to investigate the seasonality of immune response to C. albicans.Results. Upon in vitro C. albicans stimulation, 1,25(OH) 2 D 3 induced a dose-dependent, down-regulation of IL-6, TNFa, IL-17, and IFNc. It also increased IL-10 production. The shift in cytokine profile was not due to 1,25(OH) 2 D 3 augmenting expression of either Thelper differentiation factors or SOCS1 and SOCS3 mRNA. 1,25(OH) 2 D 3 inhibited TLR2, TLR4, Dectin-1, and MR mRNA and protein expression. In our seasonality study, both IL-17 and IFNc levels were suppressed in summer when 25(OH)D 3 levels were elevated.Conclusion. Vitamin D 3 skews cytokine responses toward an antiinflammatory profile, mediated by suppression of TLR2, TLR4, Dectin-1, and MR transcription, leading to reduced surface expression. The biological relevance of these effects has been confirmed by the seasonality of cytokine responses.

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1,25-Dihydroxyvitamin D3 Selectively Modulates Tolerogenic Properties in Myeloid but Not Plasmacytoid Dendritic Cells

Cited by 315 publications

References 64 publications

Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity

Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity

Trafficking properties of plasmacytoid dendritic cells in health and disease

1,25-dihydroxyvitamin D3 Modulates Cytokine Production Induced by Candida albicans: Impact of Seasonal Variation of Immune Responses

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