Vitamin D receptor ablation alters skin architecture and homeostasis of dendritic epidermal T cells

Meindl, Simone; Rot, Antal; Hoetzenecker, Wolfram; Kato, Shigeaki; Cross, Heide S.; Elbe‐Bürger, Adelheid

doi:10.1111/j.1365-2133.2005.06392.x

Cited by 16 publications

(12 citation statements)

References 55 publications

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“…VDRKO mice exhibit alopecia, develop dermal cysts, and do not recycle epidermal layers properly [21, 22]. To assess if these skin differences were involved in the differential lesion development, we performed a histological study to explore lesion architecture.…”

Section: Resultsmentioning

confidence: 99%

The Role of Vitamin D and Vitamin D Receptor in Immunity toLeishmania majorInfection

Whitcomb

DeAgostino

Ballentine

et al. 2012

Journal of Parasitology Research

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Vitamin D signaling modulates a variety of immune responses. Here, we assessed the role of vitamin D in immunity to experimental leishmaniasis infection in vitamin D receptor-deficient mice (VDRKO). We observed that VDRKO mice on a genetically resistant background have decreased Leishmania major-induced lesion development compared to wild-type (WT) mice; additionally, parasite loads in infected dermis were significantly lower at the height of infection. Enzymatic depletion of the active form of vitamin D mimics the ablation of VDR resulting in an increased resistance to L. major. Conversely, VDRKO or vitamin D-deficient mice on the susceptible Th2-biased background had no change in susceptibility. These studies indicate vitamin D deficiency, either through the ablation of VDR or elimination of its ligand, 1,25D3, leads to an increase resistance to L. major infection but only in a host that is predisposed for Th-1 immune responses.

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Section: Resultsmentioning

confidence: 99%

The Role of Vitamin D and Vitamin D Receptor in Immunity toLeishmania majorInfection

Whitcomb

DeAgostino

Ballentine

et al. 2012

Journal of Parasitology Research

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“…Human (6) and murine Langerhans cells (LC) express vitamin D receptors that may modulate their function (16). Treatment of epidermal cells with VD 3 in vitro inhibits the production of keratinocyte-derived GM-CSF, an activation factor for LCs, which results in suppression of the ability of LC to stimulate allogeneic T cell proliferation (17).…”

Section: Resultsmentioning

confidence: 99%

Expansion of Antigen-Specific Regulatory T Cells with the Topical Vitamin D Analog Calcipotriol

Ghoreishi

Bach

Obst

et al. 2009

The Journal of Immunology

131

115

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1,25-Dihydroxyvitamin D 3 is immunosuppressive both in vivo and in vitro. Topical vitamin D analogs such as calcipotriol alter keratinocyte function, but their effects on cutaneous immune responses are less well understood. We demonstrate that exposure of the skin to calcipotriol before transcutaneous immunization with OVA protein and CpG adjuvant prevents Ag-specific CD8+ T cell priming coincident with Langerhans cell depletion in the skin. Immunization through calcipotriol-treated skin induces CD4+CD25+ regulatory T cells (Treg) that prevent subsequent Ag-specific CD8+ T cell proliferation and IFN-γ production. Treg induced by calcipotriol are able to inhibit the induction and the elicitation of protein contact hypersensitivity. Topical calcipotriol treatment also induces RANKL (receptor activator of NF-κB ligand) expression by keratinocytes, a TNF family member involved in modulation of skin dendritic cells. UV light B induces Ag-specific tolerance when it is applied before transcutaneous immunization. We suggest that UV light B-induced tolerance is induced via a vitamin D receptor-dependent mechanism as vitamin D receptor (VDR) knockout mice fail to increase FoxP3+ Treg in their peripheral draining lymph node following irradiation. Additionally, keratinocytes of VDR−/− mice fail to induce RANKL upon UV irradiation or calcipotriol treatment. The in vivo expansion of Ag-specific Treg with the topical application of the vitamin D analog calcipotriol followed by transcutaneous immunization is a simple method to augment functional Ag-specific CD4+CD25+Foxp3+ Treg populations and mimics Ag-specific UV-induced tolerance.

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“…Intracellular expression of the VDR in lymph node cells from naive BALB/c mice was examined by flow cytometry using the appropriate isotype controls as previously shown (Meindl et al, 2005). Both CD4 þ CD25 þ ( Figure 4a) and CD4 þ CD25À ( Figure 4b) cells expressed the VDR intracellularly.…”

Section: Cd4 þ Cd25 þ T Cells Constitutively Express the Vitamin D Rementioning

confidence: 99%

“…An IL-2 secretion assay kit (Miltenyi Biotec) was used to determine the proportion of IL-2 secreting cells in conjunction with a Foxp3 intracellular staining kit (eBiosciences, San Diego, CA). A method previously described (Meindl et al, 2005) was used to determine intracellular VDR expression by CD4 þ CD25 ± cells using a biotinylated anti-VDR antibody (Neomarkers, Fremont, CA) or rat IgG2b isotype (BD Biosciences) with PE-Cy5-SA (BD Biosciences). Data were analyzed using FlowJo software (Tree Star, Ashland, OR).…”

Section: Facs Analysis and Antibodiesmentioning

confidence: 99%

Gene Regulation by 1,25-Dihydroxyvitamin D3 in CD4+CD25+ Cells Is Enabled by IL-2

Gorman

Judge

Hart

2010

Journal of Investigative Dermatology

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Vitamin D may be responsible for reducing the development and severity of autoimmune and allergic diseases. Topically applied 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) enhances the immunoregulatory ability of CD4+CD25+ T cells residing in the skin-draining lymph nodes (SDLNs) of mice. The mechanisms responsible were investigated by examining the expression of 84 cytokine and cytokine-related genes in a 96-well gene array. CD4+CD25+ cells isolated from the SDLNs of BALB/c mice, 24 and 96 hours after topical treatment with 1,25(OH)(2)D(3), consistently expressed increased IL-2 mRNA levels and also secreted enhanced quantities of IL-2 after ex vivo stimulation with phorbol 12-myristate 13-acetate and ionomycin. CD4+CD25+ cells from the lymph nodes of naive mice constitutively express the vitamin D receptor, allowing direct modulation by 1,25(OH)(2)D(3). However, in vitro treatment with 1,25(OH)(2)D(3) did not modify the expression of 84 tested cytokine and cytokine-related mRNAs. It was only in the presence of IL-2 that 1,25(OH)(2)D(3) increased the expression of genes including IL-2 and TLR4. Further, 1,25(OH)(2)D(3) enhanced the ability of IL-2 to stimulate CD4+CD25+ cells to proliferate in vitro and also regulate contact hypersensitivity responses on adoptive transfer into naive mice. Therefore, 1,25(OH)(2)D(3) enabled by IL-2 can directly enhance the regulatory potential of CD4+CD25+ T cells to control immune disease.

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Vitamin D receptor ablation alters skin architecture and homeostasis of dendritic epidermal T cells

Abstract: Our data imply that VDR expression controls dermal collagen production, hair development and growth, proliferation of sebaceous glands and the homeostasis of DETC. Surprisingly, VDR deficiency does not influence LC phenotype and function.

Cited by 16 publications

References 55 publications

The Role of Vitamin D and Vitamin D Receptor in Immunity toLeishmania majorInfection

The Role of Vitamin D and Vitamin D Receptor in Immunity toLeishmania majorInfection

Expansion of Antigen-Specific Regulatory T Cells with the Topical Vitamin D Analog Calcipotriol

Gene Regulation by 1,25-Dihydroxyvitamin D3 in CD4+CD25+ Cells Is Enabled by IL-2

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