Vitamin D<sub>3</sub> Induces <scp>IDO</scp><sup>+</sup> Tolerogenic <scp>DC</scp>s and Enhances Treg, Reducing the Severity of <scp>EAE</scp>

Farias, Alessandro S.; Spagnol, Gabriela Salim; Bordeaux-Rego, Pedro; Oliveira, Carlos Yure B.; Fontana, Ana Gabriela M.; Paula, Rosemeire F.O. de; Santos, Mariana P. A.; Pradella, Fernando; Moraes, Adriel S.; Oliveira, E. Capelas de; Longhini, Ana Leda; Rezende, Alexandre César Santos de; Vaisberg, Mauro; Santos, Leonilda Maria Barbosa dos

doi:10.1111/cns.12071

Cited by 124 publications

(120 citation statements)

References 42 publications

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“…The capacity of DCs, especially iDCs, to dampen autoimmune reactivity in an Ag-specific manner highlights their potential as cell-based immunotherapies (24)(25)(26)(27)(28)(29)(30)(31)(32). 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.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Interestingly, bone marrow-derived DCs cultivated in the presence of vitamin D3 have been reported to present a tolerogenic profile with high IL-10, TNF-α, and IDO expression and decreased MHC-II and CD80 expression [82]. The adoptive transfer of IDO+regDCs in rodents induced a significant increase in the percentage of CD4…”

Section: Additional Tolerogenic Pathways In Regdcs: Inosmentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory Dendritic Cells in Cancer

Shurin

2013

Cancer Microenvironment

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Three major functional subsets of dendritic cells (DCs) have been described in the tumor microenvironment in patients with cancer and tumor-bearing animals: (i) conventional DCs with intact antigen-presenting capabilities, (ii) functionally defective DCs with decreased motility and low ability to uptake, process and present antigens or produce cytokines and (iii) regulatory DCs with high capacity to suppress T cell proliferation, induce differentiation of regulatory T cells or support immune tolerance. Phenotypic characteristics of regulatory DCs (regDCs), as well as the mechanisms of T cell inhibition, vary in different experimental conditions and environments, suggesting high level of their plasticity and probably different origin. Although new data demonstrate that regDCs may play an important role at early stages of tumor development, functional differences and clinical significance of emergence of different myeloid regulatory cells (MDSCs, regDCs, M2 macrophages, N2 neutrophils, mast cells) in cancer remain to be determined.

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“…The generally recognized MS risk factor hypovitaminosis D (Ascherio & Munger, 2007;Hanwell & Banwell, 2011) is defined as a 25-hydroxyvitamin D (25(OH)D) concentration below 50 nmol/L and is prevalent in approximately 57% of German adults (Hintzpeter, Mensink, Thierfelder, Müller, & Scheidt-Nave, 2008). Experimental data show that vitamin D (VD) possesses anti-inflammatory and immunomodulatory properties through inhibition of dendritic cell differentiation, induction of T regulatory cells, blockage of Th17 differentiation, and down-regulation of Th1 immune responses (Farias et al, 2013;Hamzaoui et al, 2014;Lemire, Archer, Beck, & Spiegelberg, 1995). Concordantly, several studies have found an inverse correlation between serum 25(OH)D concentration and disease activity in MS patients (Brola et al, 2016;Pierrot-Deseilligny, Rivaud-Péchoux, Clerson, de Paz, & Souberbielle, 2012;Rotstein et al, 2015;Simpson et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D supplementation differentially affects seasonal multiple sclerosis disease activity

Miclea

Miclea²,

Pistor

et al. 2017

Brain and Behavior

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Vitamin D₃ Induces IDO⁺ Tolerogenic DCs and Enhances Treg, Reducing the Severity of EAE

Abstract: These mechanisms contribute actively to the generation of a microenvironment in the lymph nodes that suppresses the activation of encephalitogenic T cells, resulting in the downregulation of the inflammatory response in the central nervous system.

Cited by 124 publications

References 42 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

Immunosuppressive Mechanisms of Regulatory Dendritic Cells in Cancer

Vitamin D supplementation differentially affects seasonal multiple sclerosis disease activity

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Vitamin D3 Induces IDO+ Tolerogenic DCs and Enhances Treg, Reducing the Severity of EAE

Abstract: These mechanisms contribute actively to the generation of a microenvironment in the lymph nodes that suppresses the activation of encephalitogenic T cells, resulting in the downregulation of the inflammatory response in the central nervous system.

Cited by 124 publications

References 42 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

Immunosuppressive Mechanisms of Regulatory Dendritic Cells in Cancer

Vitamin D supplementation differentially affects seasonal multiple sclerosis disease activity

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Product

Resources

About

Vitamin D₃ Induces IDO⁺ Tolerogenic DCs and Enhances Treg, Reducing the Severity of EAE