1,25‐Dihydroxyvitamin D3 alters murine dendritic cell behaviour in vitro and in vivo

Ferreira, Gabriela B; Etten, Evelyne van; Verstuyf, Annemieke; Waer, Mark; Overbergh, Lut; Gysemans, Conny; Mathieu, Chantal

doi:10.1002/dmrr.1275

Cited by 91 publications

(69 citation statements)

References 48 publications

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“…However, clinical applications of DC-based therapies in autoimmune disease intervention are hampered by the concern that iDCs will develop into immunostimulatory cells upon encountering inflammatory stimuli in vivo. In this sense, we (9,14,18) and other investigators (6,7,12) showed that mDCs differentiated and matured in vitro in the presence of the biologically active form of vitamin D, 1,25(OH) 2 D 3 , produced a stable phenotype, typically characterized by low levels of Ag-presenting and costimulatory molecules (MHCII, CD80, CD86), as well as a high ratio of PD-L1/CD86 and anti-inflammatory cytokines (IL-10, TGF-b). In this study, we further demonstrated the capacity of 1,25(OH) 2 D 3 to imprint a similar tolerogenic profile in mDCs derived from diabetes-prone mice and diabetes-resistant animals.…”

Section: Discussionmentioning

confidence: 97%

“…BM-derived DCs were obtained in vitro, as previously described (18). Briefly, BM was isolated from long bones of C57BL/6 or NOD mice aged 4-5 wk.…”

Section: In Vitro Generation Of Bm-derived Murine Dcsmentioning

confidence: 99%

“…This introduces a potential flaw in studies presenting drug effects on DCs, especially when using only nonautoimmune donors. In this regard, we (18)(19)(20) showed that modulation of the DC phenotype is possible in bone marrow (BM)-derived DCs from C57BL/6 or NOD mice, but data on the functionality of these cells are lacking or incomplete.…”

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confidence: 99%

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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

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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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Section: Discussionmentioning

confidence: 97%

“…BM-derived DCs were obtained in vitro, as previously described (18). Briefly, BM was isolated from long bones of C57BL/6 or NOD mice aged 4-5 wk.…”

Section: In Vitro Generation Of Bm-derived Murine Dcsmentioning

confidence: 99%

See 1 more Smart Citation

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

Self Cite

114

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“…BMDCs were generated from 3 to 4 week-old mice according to a previously established protocol [6,18]. Briefly, bone marrow precursors were cultured in RPMI 1640 medium (Life Technologies, Rockville, MD, USA) supplemented with Glutamax-I, 25 mM HEPES, 10% heat-inactivated fetal calf serum (FCS) (Thermo Scientific, Sunnyvale, CA, USA), 50 mM 2-mecraptoethanol (2-ME) (UCB, Brussels, Belgium) and 100 U/ml Penicillin/Streptomycin in the presence of 20 ng/ml murine recombinant IL-4 and 20 ng/ml murine recombinant GM-CSF (Peprotech, Rocky Hill, NJ, USA) for 8 days.…”

Section: Generation Of Myeloid Dcsmentioning

confidence: 99%

“…granulocyte macrophage colony stimulating factor (GM-CSF)/interleukin (IL)-4 [myeloid or conventional DCs] and Flt-3 ligand [plasmacytoid DCs]). Upon binding of 1a,25(OH) 2 D 3 to the VDR, both the differentiation and maturation of particularly myeloid DCs will be inhibited, leading to reduced cell surface expression of CD40, CD80, and CD86 costimulatory molecules, reduced T cell stimulatory function, and decreased survival [6,7].…”

Section: Introductionmentioning

confidence: 99%

The phenotype and function of murine bone marrow-derived dendritic cells is not affected by the absence of VDR or its ability to bind 1α,25-dihydroxyvitamin D3

Vanherwegen

Ferreira

Smeets

et al. 2016

The Journal of Steroid Biochemistry and Molecular Biology

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The nuclear vitamin D receptor (VDR) is generally recognized as a ligand-dependent transcription factor that mediates the actions of its natural ligand, 1a,25-dihydroxyvitamin D 3 (1a,25(OH) 2 D 3 ) on multiple target genes involved in mineral homeostasis, bone development, as well as immune reactivity. As the VDR is widely distributed in nearly all cells of the body, it implies that the vitamin D endocrine system may regulate many cell types and functions. Experiments in VDR null mice established that the VDR has intrinsically critical roles in skin and keratinocyte biology but not in immune responses. Oppositely, absence of the VDR ligand is linked to susceptibility to autoimmunity, illustrating a potential role for the unliganded VDR in the immune system. This discrepancy stimulated us to further investigate the impact of the VDR on the phenotype and function of myeloid dendritic cells (DCs) generated ex vivo from bone marrow precursors of VDR null (with a truncated VDR) and VDR DAF2 mice (with a mutated C-terminal activation factor 2 domain thus rendering ligand-induced gene transcription impossible). Absent or unliganded VDR did not affect bone marrow-derived myeloid DC generation. DCs obtained from VDR null and VDR DAF2 bone marrow cells had comparable MHC-II, and costimulatory molecule CD86, CD80 and CD40 expression than DCs from wild-type bone marrow cells. Additionally, an unliganded VDR did not affect the cytokine production nor the antigen-specific T cell stimulatory capacity of bone marrowderived DCs. In conclusion, we showed that although clear effects of 1a,25-dihydroxyvitamin D 3 are described on DC generation, absence of VDR or presence of an unliganded VDR does not affect the profile and function of ex vivo generated bone marrow-derived DCs.

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Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti‐Inflammatory

et al. 2020

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Regulation of immune function continues to be one of the most well-recognized extraskeletal actions of vitamin D. This stemmed initially from the discovery that antigen presenting cells such as macrophages could actively metabolize precursor 25-hydroxyvitamin D (25D) to active 1,25-dihydroxyvitamin D (1,25D). Parallel observation that activated cells from the immune system expressed the intracellular vitamin D receptor (VDR) for 1,25D suggested a potential role for vitamin D as a localized endogenous modulator of immune function. Subsequent studies have expanded our understanding of how vitamin D exerts effects on both the innate and adaptive arms of the immune system. At an innate level, intracrine synthesis of 1,25D by macrophages and dendritic cells stimulates expression of antimicrobial proteins such as cathelicidin, as well as lowering intracellular iron concentrations via suppression of hepcidin. By potently enhancing autophagy, 1,25D may also play an important role in combatting intracellular pathogens such as M. tuberculosis and viral infections. Local synthesis of 1,25D by macrophages and dendritic cells also appears to play a pivotal role in mediating T-cell responses to vitamin D, leading to suppression of inflammatory T helper (Th)1 and Th17 cells, and concomitant induction of immunotolerogenic Tregulatory responses. The aim of this review is to provide an update on our current understanding of these prominent immune actions of vitamin D, as well as highlighting new, less well-recognized immune effects of vitamin D. The review also aims to place this mechanistic basis for the link between vitamin D and immunity with studies in vivo that have explored a role for vitamin D supplementation as a strategy for improved immune health. This has gained prominence in recent months with the global coronavirus disease 2019 health crisis and highlights important new objectives for future studies of vitamin D and immune function.

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1,25‐Dihydroxyvitamin D₃ alters murine dendritic cell behaviour in vitro and in vivo

Abstract: We conclude that in vitro 1,25(OH)2D3 exposure alters dendritic cell behaviour, converting them into a cell type that drives T cells away from destruction towards a regulatory phenotype.

Cited by 91 publications

References 48 publications

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

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

The phenotype and function of murine bone marrow-derived dendritic cells is not affected by the absence of VDR or its ability to bind 1α,25-dihydroxyvitamin D3

Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti‐Inflammatory

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