Potent Inhibition of Dendritic Cell Differentiation and Maturation by Vitamin D Analogs

Griffin, Matthew D.; Lutz, Ward; Phan, Vy; Bachman, Lori A.; McKean, David J.; Kumar, Rajiv

doi:10.1006/bbrc.2000.2490

Cited by 250 publications

(171 citation statements)

References 35 publications

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“…Interestingly, we have demonstrated no effect on CD40 expression in our system, in analogy to previous reports [16], while in other systems a suppression of this molecule was observed [17,26]. A common feature of all systems is an almost complete suppression of IL-12 secretion by 1a,25(OH) 2 D 3 [18].…”

Section: Discussionsupporting

confidence: 88%

1α,25-Dihydroxyvitamin D3 modulates the murine antibody response to pneumococcal capsular polysaccharide serotype 3 through IL-12

Jeurissen¹,

Etten²,

Overbergh³

et al. 2005

Eur. J. Immunol.

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1a, 25(OH) 2 D 3 ] is a steroid hormone that regulates calcium metabolism. Besides, 1a,25(OH) 2 D 3 also has pronounced immunomodulatory effects: it strongly inhibits dendritic cell (DC) maturation and impairs IL-12 production. We studied the effect of 1a,25(OH) 2 D 3 on the antibody response to pneumococcal capsular polysaccharide (caps-PS) serotype 3. 1a,25(OH) 2 D 3 inhibited the IgG2a antibody response to caps-PS serotype 3. Besides, 1a,25(OH) 2 D 3 also inhibited IL-12 production and maturation of DC. Anti-IL-12 and exogenous IL-12, respectively, inhibited and stimulated the IgG2a antibody response to caps-PS serotype 3. Exogenous IL-12 abrogated the effect of 1a,25(OH) 2 D 3 on the IgG2a antibody response to caps-PS serotype 3, indicating that the effect of 1a,25(OH) 2 D 3 on the IgG2a antibody response to caps-PS serotype 3 was mediated through IL-12.In conclusion, we demonstrate that 1a,25(OH) 2 D 3 has an inhibitory effect on the IgG2a antibody response to caps-PS serotype 3, and that this effect was mediated trough IL-12.

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Section: Discussionsupporting

confidence: 88%

1α,25-Dihydroxyvitamin D3 modulates the murine antibody response to pneumococcal capsular polysaccharide serotype 3 through IL-12

Jeurissen¹,

Etten²,

Overbergh³

et al. 2005

Eur. J. Immunol.

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“…These include vitamin D. The biologically active form of this vitamin, 1␣,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) (or its analogues), can block both monocyte differentiation into DC and the activation of DC (51)(52)(53)(54)(55) at least in part by inhibition of the NF-B pathway (56,57). T cells exposed to 1,25(OH) 2 D 3 -treated DC are unresponsive (58,59), may undergo apoptosis (58 -60), can be anergic to subsequent stimulation with Ag (51,59,61), and can adopt a regulatory phenotype (59,61).…”

Section: Discussionmentioning

confidence: 99%

“…T cells exposed to 1,25(OH) 2 D 3 -treated DC are unresponsive (58,59), may undergo apoptosis (58 -60), can be anergic to subsequent stimulation with Ag (51,59,61), and can adopt a regulatory phenotype (59,61). Unlike vitamins C and E, 1,25(OH) 2 D 3 is a steroid, and its operation is through a specific receptor, as shown by its lack of action in (murine) DC lacking vitamin D receptors (51,52).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of NF-κB and Oxidative Pathways in Human Dendritic Cells by Antioxidative Vitamins Generates Regulatory T Cells

Tan

Sagoo

Chan

et al. 2005

The Journal of Immunology

193

153

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Dendritic cells (DCs) are central to T cell immunity, and many strategies have been used to manipulate DCs to modify immune responses. We investigated the effects of antioxidants ascorbate (vitamin C) and α-tocopherol (vitamin E) on DC phenotype and function. Vitamins C and E are both antioxidants, and concurrent use results in a nonadditive activity. We have demonstrated that DC treated with these antioxidants are resistant to phenotypic and functional changes following stimulation with proinflammatory cytokines. Following treatment, the levels of intracellular oxygen radical species were reduced, and the protein kinase RNA-regulated, eukaryotic translation initiation factor 2α, NF-κB, protein kinase C, and p38 MAPK pathways could not be activated following inflammatory agent stimulation. We went on to show that allogeneic T cells (including CD4+CD45RO, CD4+CD45RA, and CD4+CD25− subsets) were anergized following exposure to vitamin-treated DCs, and secreted higher levels of Th2 cytokines and IL-10 than cells incubated with control DCs. These anergic T cells act as regulatory T cells in a contact-dependent manner that is not dependent on IL-4, IL-5, IL-10, IL-13, and TGF-β. These data indicate that vitamin C- and E-treated DC might be useful for the induction of tolerance to allo- or autoantigens.

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“…It has been demonstrated that pharmacological doses of the functional metabolite of vitamin D, 1␣,25-dihydroxyvitamin D 3 [1,25-(OH) 2 D 3 ], can greatly reduce or eliminate the incidence and progression of EAE in mice (12,13). In addition, 1,25-(OH) 2 D 3 has been shown to be an inhibitor of activated T cells both in vivo and in vitro and a modulator of antigen-presenting cells (14)(15)(16).…”

mentioning

confidence: 99%

CD8⁺T cells are not necessary for 1α,25-dihydroxyvitamin D₃to suppress experimental autoimmune encephalomyelitis in mice

Meehan

DeLuca

2002

Proc. Natl. Acad. Sci. U.S.A.

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In addition to its role in calcium and phosphorous homeostasis, 1␣,25-dihydroxyvitamin D3 [1,25-(OH)2D3] appears to be a modulator of the immune system. Administration of 1,25-(OH) 2D3 prevents disease in several autoimmune animal models, including experimental autoimmune encephalomyelitis (EAE). The vitamin D receptor is believed to mediate this activity. Among cells of the immune system, CD8 ؉ T cells have the highest levels of the vitamin D receptor. Because CD8 ؉ T cells have been implicated as both suppressors and effectors of the inflammation associated with multiple sclerosis and EAE, we examined the question of whether the 1,25-(OH) 2D3 suppression of EAE occurs through a CD8 ؉ T cell-dependent mechanism. To test this hypothesis, mice that are homozygous knockouts for the ␣ chain of the CD8 receptor and have been characterized as lacking functional CD8 ؉ T cells (CD8 ؉ ؊͞؊) were provided 1,25-(OH)2D3 in their diet before EAE induction. Although CD8 ؉ ؊͞؊ mice fed the same diet lacking 1,25-(OH) 2D3 have a high incidence of EAE, EAE did not occur in CD8 ؉ ؊͞؊ mice fed the diet containing 1,25-(OH)2D3. We conclude that CD8 ؉ T cells neither are needed nor do they play a role in the prevention of EAE by 1,25-(OH) 2D3.M ultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that is the leading cause of disease-associated neurological disability in western countries (1). This disease is characterized by destruction of the myelin sheaths that surround axons in the central nervous system and ultimately results in numerous neurological defects that manifest in symptoms including fatigue, limb spasticity, bladder dysfunction, and muscle weakness so severe that death is sometimes the result (2, 3). This inflammation is caused by either a breakdown in immunological self tolerance and͞or an infection that triggers central nervous system-specific T cells to form inflammatory lesions. Although very little is known about the triggering event for MS, it is clear that both environmental and genetic factors are involved (4). In examining environmental factors, the geographical distribution of MS must be considered. A north-to-south gradient of higher-to-lower MS incidence in the northern hemisphere has been demonstrated in epidemiology studies, whereas a similar gradient running south to north has been observed in the southern hemisphere (5, 6). In 1974, P. Goldberg noted that this MS incidence gradient correlated with the incidence of vitamin D deficiency in temperate regions, relative to equatorial regions (7). Further studies demonstrated a lower MS incidence in temperate areas where vitamin D is abundant because of increased sun exposure, high altitudes, or diets rich in fish oils (8)(9)(10)(11).Insights into the disease course of MS have been found by using the animal model experimental autoimmune encephalomyelitis (EAE). EAE is a CD4 ϩ T cell-mediated inflammatory demylenating disease that shares many similarities with MS and is induced by injecting an antigen such as myelin basic pro...

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Potent Inhibition of Dendritic Cell Differentiation and Maturation by Vitamin D Analogs

Cited by 250 publications

References 35 publications

1α,25-Dihydroxyvitamin D3 modulates the murine antibody response to pneumococcal capsular polysaccharide serotype 3 through IL-12

1α,25-Dihydroxyvitamin D3 modulates the murine antibody response to pneumococcal capsular polysaccharide serotype 3 through IL-12

Inhibition of NF-κB and Oxidative Pathways in Human Dendritic Cells by Antioxidative Vitamins Generates Regulatory T Cells

CD8⁺T cells are not necessary for 1α,25-dihydroxyvitamin D₃to suppress experimental autoimmune encephalomyelitis in mice

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Potent Inhibition of Dendritic Cell Differentiation and Maturation by Vitamin D Analogs

Cited by 250 publications

References 35 publications

1α,25-Dihydroxyvitamin D3 modulates the murine antibody response to pneumococcal capsular polysaccharide serotype 3 through IL-12

1α,25-Dihydroxyvitamin D3 modulates the murine antibody response to pneumococcal capsular polysaccharide serotype 3 through IL-12

Inhibition of NF-κB and Oxidative Pathways in Human Dendritic Cells by Antioxidative Vitamins Generates Regulatory T Cells

CD8+T cells are not necessary for 1α,25-dihydroxyvitamin D3to suppress experimental autoimmune encephalomyelitis in mice

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CD8⁺T cells are not necessary for 1α,25-dihydroxyvitamin D₃to suppress experimental autoimmune encephalomyelitis in mice