Vitamin D3 targets epidermal and dermal dendritic cells for induction of distinct regulatory T cells

Aar, Angelic M. G. van der; Sibiryak, Darya S.; Bakdash, Ghaith; Capel, Toni M.M. van; Kleij, Hanneke P. M. van der; Opstelten, Dirk-Jan E.; Teunissen, Marcel B. M.; Kapsenberg, Martien L.; Jong, Esther C. de

doi:10.1016/j.jaci.2011.01.068

Cited by 139 publications

(135 citation statements)

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“…2B). In contrast to our earlier findings with isolated skin DCs and LCs in vitro, 21 ID-injected VitD was not able to inhibit LPS-induced maturation. On the contrary, VitD supported LPS-induced DC maturation by slightly upregulating the expression of CD86 in the CD14 + DDC subset and CD83 expression in the CD1a + DDC subset ( Fig.…”

Section: Introductioncontrasting

confidence: 99%

“…17,18 Furthermore, VitD renders DCs tolerogenic by downregulating the synthesis of IL-12, while boosting IL-10 secretion and inducing the expression of ILT3 and PD-L1, altogether leading to Treg priming and inhibiting Th1 cell development. [19][20][21] Furthermore, VitD induces the expression of skin epidermal homing receptor CCR10 on T cells, which guides these cells to the epidermis. 22 The skin is an interesting site for vaccination as it is equipped with an extensive network of DCs.…”

Section: Introductionmentioning

confidence: 99%

“…VitD is able to block the maturation of monocyte-derived DDCs and LCs. 21 In order to determine whether VitD maintained this capacity when injected directly in the skin, we determined the CD83 and CD86 expression on the different DC subsets. Regardless of the injected compounds, the CD14 + DDC subset always appeared less mature compared with LCs and CD1a + DDCs, as reflected by the lower expression of both CD86 and CD83 ( Fig.…”

Section: Introductionmentioning

confidence: 99%

“…The levels of IL-6, IL-10, IL-12 and TNF-α, the last three known to be modulated by VitD, 21 were determined in the medium surrounding the biopsies after 72 h of injection. Injected VitD slightly reduced LPSinduced IL-6 production, yet this reduction was insignificant.…”

Section: Introductionmentioning

confidence: 99%

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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

Bakdash

Schneider

Capel

et al. 2013

Human Vaccines & Immunotherapeutics

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Section: Introductioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Bakdash

Schneider

Capel

et al. 2013

Human Vaccines & Immunotherapeutics

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“…Our data point to the expansion of preexisting Tregs, rather than the conversion from naive CD4 + T cells, because 1,25D 3 -mDCs failed to reproduce the characteristic increase in Treg frequency in vitro following coculture with CD25-depleted CD4 + T cells. In contrast, different groups (11,12,53) (54). In addition to pointing to the expansion of Tregs, our data show that CD4 + CD25 + Tregs expanded in the presence of 1,25D 3 -mDCs featured elevated levels of regulatory mediators, such as IL-10, which might be relevant for their increased suppressive function in vivo.…”

Section: Discussionmentioning

confidence: 54%

1,25-Dihydroxyvitamin D3 Promotes Tolerogenic Dendritic Cells with Functional Migratory Properties in NOD Mice

Ferreira

Gysemans

Demengeot

et al. 2014

The Journal of Immunology

114

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The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is able to promote the generation of tolerogenic mature dendritic cells (mDCs) with an impaired ability to activate autoreactive T cells. These cells could represent a reliable tool for the promotion or restoration of Ag-specific tolerance through vaccination strategies, for example in type 1 diabetes patients. However, successful transfer of 1,25(OH)2D3-treated mDCs (1,25D3-mDCs) depends on the capacity of 1,25(OH)2D3 to imprint a similar tolerogenic profile in cells derived from diabetes-prone donors as from diabetes-resistant donors. In this study, we examined the impact of 1,25(OH)2D3 on the function and phenotype of mDCs originating from healthy (C57BL/6) and diabetes-prone (NOD) mice. We show that 1,25(OH)2D3 is able to imprint a phenotypic tolerogenic profile on DCs derived from both mouse strains. Both NOD- and C57BL/6-derived 1,25D3-mDCs decreased the proliferation and activation of autoreactive T cells in vitro, despite strain differences in the regulation of cytokine/chemokine expression. In addition, 1,25D3-mDCs from diabetes-prone mice expanded CD25+Foxp3+ regulatory T cells and induced intracellular IL-10 production by T cells in vitro. Furthermore, 1,25D3-mDCs exhibited an intact functional migratory capacity in vivo that favors homing to the liver and pancreas of adult NOD mice. More importantly, when cotransferred with activated CD4+ T cells into NOD.SCID recipients, 1,25D3-mDCs potently dampened the proliferation of autoreactive donor T cells in the pancreatic draining lymph nodes. Altogether, these results argue for the potential of 1,25D3-mDCs to restore Ag-specific immune tolerance and arrest autoimmune disease progression in vivo.

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Regulation of CYP27B1 and CYP24A1 hydroxylases limits cell‐autonomous activation of vitamin D in dendritic cells

et al. 2014

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Keywords: CYP27B1 r CYP24A1 r DCs r Macrophages r Vitamin D Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionThe capacity of vitamin D metabolites to modulate macrophage and DC function has been subject to extensive research interest in light of the association of vitamin D deficiency with a broad spectrum of immunological and infectious diseases. This gives Correspondence: Dr. Mahdad Noursadeghi e-mail: m.noursadeghi@ucl.ac.uk way to the potential for vitamin D supplementation [1][2][3][4] or ex vivo conditioning of DCs with vitamin D for cell therapy strategies [5]. Vitamin D is synthesized from 7-dehydrocholesterol in the skin following exposure to ultraviolet B radiation and thermal isomerisation, or replenished by dietary intake. It is 25-hydroxylated in the liver to form 25-hydroxyvitamin D (25[OH]D), which is in * These authors contributed equally to this work. Results 25[OH]D is not functionally activated during monocyte differentiation to immature DCsWe first compared the activation of 25[OH]D during monocyte differentiation into macrophages and immature DCs. Conventional cell culture media in this model are vitamin D deficient (Fig. 1A) (Fig. 1B). This was also associated with upregulation of the prototypic vitamin D-inducible gene cathelicidin (CAMP) in macrophages (Fig. 1C) (Fig. 1C). Importantly, upregulation of DC-SIGN during monocyte differentiation to DCs was not affected by the presence of 1,25[OH] 2 D (Fig. 1D) DCs show time-dependent increase in activation of 25[OH]D independent of CYP27B1 expression levelsWe confirmed previous observations [16] that expression of the vitamin D-activating hydroxylase CYP27B1 is significantly lower in DCs compared with MDMs at both transcript and protein levels ( Fig. 2A and B). In contrast, vitamin D receptor (VDR) expression was higher in DCs than MDMs ( Fig. 2A). Taken together, these data further support the hypothesis that 25[OH]D has no effect on DCs in the experiments described above, because of a failure to generate 1,25[OH] 2 D rather than an inability to respond to 1,25[OH] 2 D. We also confirmed that 24-h stimulation of DCs with LPS significantly increases transcript and protein levels of CYP27B1 ( Fig. 2B and C (Fig. 2D). However, there was no concomitant upregulation of CAMP (Fig. 2C) . Monocytes are typically differentiated to DCs over 4-7 days, therefore we considered the possibility that time in culture may confound comparisons between different studies. Interestingly, we did find 25[OH]D-dependent upregulation of CAMP gene expression in DCs that increased with time after at least 6 days in culture (Fig. 2E). This was not associated with any significant time-dependent increase in CYP27B1 expression ( DCs express truncated CYP27B1 transcriptsWe found that LPS stimulation was able to upregulate DC expression of CYP27B1 transcript to levels higher than that in MDMs ( Figs. 2A and C). However, the expression of CYP27B1 protein remains much lower in DCs compared with ...

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Vitamin D3 targets epidermal and dermal dendritic cells for induction of distinct regulatory T cells

Cited by 139 publications

References 37 publications

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

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

1,25-Dihydroxyvitamin D3 Promotes Tolerogenic Dendritic Cells with Functional Migratory Properties in NOD Mice

Regulation of CYP27B1 and CYP24A1 hydroxylases limits cell‐autonomous activation of vitamin D in dendritic cells

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Vitamin D3 targets epidermal and dermal dendritic cells for induction of distinct regulatory T cells

Cited by 139 publications

References 37 publications

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

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

1,25-Dihydroxyvitamin D3 Promotes Tolerogenic Dendritic Cells with Functional Migratory Properties in NOD Mice

Regulation of CYP27B1 and CYP24A1 hydroxylases limits cell‐autonomous activation of vitamin D in 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

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