Intradermal application of vitamin D3 increases migration of CD14<sup>+</sup>dermal dendritic cells and promotes the development of Foxp3<sup>+</sup>regulatory T cells

Bakdash, Ghaith; Schneider, Laura P.; Capel, Toni M.M. van; Kapsenberg, Martien L.; Teunissen, Marcel B. M.; Jong, Esther C. de

doi:10.4161/hv.22918

Cited by 30 publications

(44 citation statements)

References 49 publications

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“…The innovative concept of endogenous AMP induction as a novel, anti-infective strategy has shown to be promising [13,25] but remains to be investigated in detail. It has been shown extensively that VitD 3 and its analogs are able to induce a DC subset that appears to be immature and has tolerogenic capabilities associated with T reg cell induction, T cell anergy, and effector T cell death [15][16][17]. Despite that VitD 3 is known for its cathelicidin-inducing properties, so far, no one has investigated the antimicrobial activities of this DC subset.…”

Section: Discussionmentioning

confidence: 99%

“…For example, the VitD 3 /PBA-differentiated DCs resemble a subset of dermal DCs [31] that were shown to be more efficient in recognizing pathogens than other DC subsets in the skin. Interestingly, Bakdash et al [15] showed that intradermally applied VitD 3 increased the migration of tolerogenic CD14 ϩ dermal DCs, promoting T reg development. Lastly, a macrophage-like CD14 ϩ CD1a-DC subset was shown in a human skin explant model that displayed poor T cell-stimulatory abilities [32].…”

Section: Discussionmentioning

confidence: 99%

“…Besides the induction of cathelicidin expression, VitD 3 and PBA display an array of additional immunomodulatory functions [6], and thus, it is of interest to investigate how these effects contribute to bacterial clearance and to establish to what extent such effects are dependent on cathelicidin induction. Several studies have shown modulating effects of VitD 3 on DC differentiation and that the resulting DC subset displays specific T cell-stimulatory capacity [15][16][17]. None, however, have investigated their antimicrobial activities.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D3 and phenylbutyrate promote development of a human dendritic cell subset displaying enhanced antimicrobial properties

Does

Kenne

Koppelaar

et al. 2014

Journal of Leukocyte Biology

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A promising strategy in the fight against multidrug-resistant pathogens is the induction of endogenous AMPs, with compounds such as VitD₃ and PBA. These compounds display an array of immunomodulatory effects that remain to be investigated in further detail to establish their role in the clearance of infection and possible modulation of AMP expression. Here, we have investigated the effects of VitD₃ and PBA on human monocyte-DC differentiation and found that VitD₃ and PBA promote the development of a stretched CD14⁺/CD1a⁻ DC subset. This subset produced enhanced levels of ROS and human cathelicidin; furthermore, it displayed enhanced killing capacity of Staphylococcus aureus compared with control DCs. When experiments were performed in WT and cathelicidin-deficient mice, we established that a ROS-producing, stretched DC subset was also induced in mouse-derived cells, independent of cathelicidin expression. However, in contrast to the human DCs, enhanced cathelicidin expression and enhanced antimicrobial activities were not found in the murine VitD₃/PBA DC subset. In conclusion, the results of this study show that VitD₃ and PBA induce a human DC subset that is effective against infection. These results promote further research into the use of these compounds as an antimicrobial treatment strategy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Vitamin D3 and phenylbutyrate promote development of a human dendritic cell subset displaying enhanced antimicrobial properties

Does

Kenne

Koppelaar

et al. 2014

Journal of Leukocyte Biology

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“…We were surprised that neither topical treatment with vitamin D nor vitamin A appeared to promote a regulatory phenotype in LCs. Vitamin D has been reported to induce regulatory potential when used to treat psoriatic skin, when used to locally target dermal DCs in skin explants and in combination with steroid to treat mature monocyte‐derived DCs . DCs used in the skin blister model are mainly of epidermal origin and therefore likely to exhibit an immature phenotype .…”

Section: Discussionmentioning

confidence: 99%

Topical steroid therapy induces pro‐tolerogenic changes in Langerhans cells in human skin

et al. 2015

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We have investigated the efficacy of conditioning skin Langerhans cells (LCs) with agents to promote tolerance and reduce inflammation, with the goal of improving the outcomes of antigen-specific immunotherapy. Topical treatments were assessed ex vivo, using excised human breast skin maintained in organ bath cultures, and in vivo in healthy volunteers by analysing skin biopsies and epidermal blister roof samples. Following topical treatment with a corticosteroid, tumour necrosis factor-α levels were reduced in skin biopsy studies and blister fluid samples. Blister fluid concentrations of monocyte chemoattractant protein-1, macrophage inflammatory proteins -1α and 1β and interferon-γ inducible protein-10 were also reduced, while preserving levels of interleukin-1α (IL-1α), IL-6, IL-8 and IL-10. Steroid pre-treatment of the skin reduced the ability of LCs to induce proliferation, while supernatants showed an increase in the IL-10/interferon-γ ratio. Phenotypic changes following topical steroid treatment were also observed, including reduced expression of CD83 and CD86 in blister-derived LCs, but preservation of the tolerogenic signalling molecules immunoglobulin-like transcript 3 and programmed death-1. Reduced expression of HLA-DR, CD80 and CD86 were also apparent in LCs derived from excised human skin. Topical therapy with a vitamin D analogue (calcipotriol) and steroid, calcipotriol alone or vitamin A elicited no significant changes in the parameters studied. These experiments suggest that pre-conditioning the skin with topical corticosteroid can modulate LCs by blunting their pro-inflammatory signals and potentially enhancing tolerance. We suggest that such modulation before antigen-specific immunotherapy might provide an inexpensive and safe adjunct to current approaches to treat autoimmune diseases.

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“…74 In related studies of a human skin explant model, intradermally injected 1,25-OH-VD3 increased the migration of dermal CD14 + DC, a monocyte-derived DC population, 76 while repressing the T-cell stimulatory capacities of total migrating DC. 77 Hence, the presence of 1,25-OH-VD3 during DC activation shapes their migratory capacity upon antigen uptake, and potentially modulates the scope of their induced T-cell responses not with respect to antigen specificity, but rather to T-cell skewing and trafficking potential. 1,25-OH-VD3 regulation of DC migratory properties during antigen responses may therefore represent an additional mechanism for regulation of immune responses by local VD3 metabolism.…”

Section: Vd3 Influences the Migratory Patterns Of DCmentioning

confidence: 99%

Vitamin D immunoregulation through dendritic cells

2016

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SummaryVitamin D (VD3) has been linked to immunological processes, and its supplementation may have a role in treatment or prevention of diseases with underlying autoimmune or pro‐inflammatory states. As initiators of the immune responses, dendritic cells (DC) are a potential target of VD3 to dampen autoimmunity and inflammation, but the role of DC in VD3‐mediated immunomodulation in vivo is not understood. In addition to being targets of VD3, DC can provide a local source of bioactive VD3 for regulation of T‐cell responses. Here we review existing studies that describe the tolerogenic potential of VD3 on DC, and discuss them in the context of current understanding of DC development and function. We speculate on mechanisms that might account for the potent but poorly understood tolerogenic activities of VD3 and the role of DC as both targets and sources of this hormone.

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Intradermal application of vitamin D3 increases migration of CD14⁺dermal dendritic cells and promotes the development of Foxp3⁺regulatory T cells

Cited by 30 publications

References 49 publications

Vitamin D3 and phenylbutyrate promote development of a human dendritic cell subset displaying enhanced antimicrobial properties

Vitamin D3 and phenylbutyrate promote development of a human dendritic cell subset displaying enhanced antimicrobial properties

Topical steroid therapy induces pro‐tolerogenic changes in Langerhans cells in human skin

Vitamin D immunoregulation through dendritic cells

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Intradermal application of vitamin D3 increases migration of CD14+dermal dendritic cells and promotes the development of Foxp3+regulatory T cells

Cited by 30 publications

References 49 publications

Vitamin D3 and phenylbutyrate promote development of a human dendritic cell subset displaying enhanced antimicrobial properties

Vitamin D3 and phenylbutyrate promote development of a human dendritic cell subset displaying enhanced antimicrobial properties

Topical steroid therapy induces pro‐tolerogenic changes in Langerhans cells in human skin

Vitamin D immunoregulation through dendritic cells

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Intradermal application of vitamin D3 increases migration of CD14⁺dermal dendritic cells and promotes the development of Foxp3⁺regulatory T cells