Induction of regulatory dendritic cells by dexamethasone and 1α,25-Dihydroxyvitamin D3

Pedersen, Anders Elm; Gad, Monika; Walter, Mark R.; Claësson, Mogens H.

doi:10.1016/j.imlet.2003.11.004

Cited by 78 publications

(60 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…DEXAMETHASONE AND NEONATAL DENDRITIC CELLS a counterbalancing Th1 cytokine, confirms the work of others (29,33,34,44). The observation that Dx added to CB cells during the differentiation stage dramatically amplified the modulation compared with AB cells extends previous observations (Fig.…”

supporting

confidence: 90%

“…Glucocorticoids have been shown to inhibit maturation of murine DCs (24) by reducing the expression of adhesion molecules and co-stimulatory molecules, resulting in diminished priming and activation of specific T cells (25,26) or up-regulation of IL-10 secreting T regulatory cells (27). Cultured adult human cells that are treated with glucocorticoids decrease expression of DC co-stimulatory molecules (29,32), retard DC differentiation and maturation (29 -32), alter DC endocytic function, and weaken DC immunostimulatory capacity in antigen presentation to autologous T cells (29,30,33,35,36). Our study confirmed most of these effects on AB DCs but, more important, showed a greater impact of Dx on monocyte-derived DCs from neonatal than adult blood cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Dexamethasone Inhibits Maturation and Alters Function of Monocyte-Derived Dendritic Cells from Cord Blood

2005

View full text Add to dashboard Cite

Critically ill infants are treated with dexamethasone (Dx) and other glucocorticoids to reduce inflammation and to promote lung and cardiac function. The neonatal immune system is immature, so neonatal dendritic cells (DCs) might be especially sensitive to glucocorticoid-mediated immunosuppression. To test this, we compared Dx treatment of monocyte-derived DCs from cord (CB) and adult blood (AB). Dx decreased CD1a levels on both AB and CB DCs. CB-treated cells also exhibited decreased expression of CD83 and increased expression of CD14, alterations not observed in AB DCs. Characteristic immature endocytic activity was sustained and enhanced in Dx-treated CB DCs, whereas AB DCs matured normally. Maintenance of endocytosis corresponded with CD14 expression. Dx markedly increased CB DC IL-10, a T cell helper 2 (Th2)-preferential cytokine, while reducing IL-12, a counterbalancing Th1 cytokine. AB DCs were also affected, but increases in IL-10 and decreases in IL-12 were more modest. Dx treatment also inhibited DC-induced T cell proliferation, but CB DCs were inhibited more. In short, neonatal DCs seemed to be especially sensitive to the immunosuppressive effects of Dx as indicated by altered phenotype, endocytic function, ability to stimulate T cells, and cytokine shift favoring Th2. These alterations in DC function are consistent with an increased risk for certain infections and atopic diseases. Cytokines that are produced by the placenta dampen allograft rejection and are thought to enhance the intrauterine survival of the fetus (1). This immune attenuation tends to direct an immune response toward T helper (Th) 2 and to weaken development of Th1-mediated immunity in newborns (2). The full range of adaptive immunity is gradually acquired through exposure to antigens that induce Th1 T cell responses and the development of a balanced immune system. When mothers go into premature labor, glucocorticoids, such as dexamethasone (Dx), are widely prescribed to enhance fetal lung maturation (3). In addition, glucocorticoids are used postnatally to reduce lung inflammation and to improve cardiovascular status in critically ill infants (4). Dx-treated infants have alterations in immune responsiveness as indicated by significantly reduced antibody responses after immunization (5); increased infections (6); multiple short-term adverse complications such as intestinal perforation (7-9), hypertension, and hypertrophic cardiomyopathy (10,11); and long-term effect such as increased risk for airway hyperresponsiveness and decreased pulmonary function (12,13).Several in vitro studies that were designed to identify the stage of maturation of each immune cell lineage in normal newborns have revealed that neonate naïve T (14 -16) and B (17,18)

show abstract

supporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Dexamethasone Inhibits Maturation and Alters Function of Monocyte-Derived Dendritic Cells from Cord Blood

2005

View full text Add to dashboard Cite

show abstract

“…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). 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

197

159

View full text Add to dashboard Cite

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.

show abstract

“…Treatment of DCs with 1␣,25-dihydroxyvitamin D 3 (vitamin D 3 ) in combination with dexamethasone has been shown to synergistically inhibit lipopolysaccharide (LPS)-induced maturation of DCs (24). Previously, we used these immunosuppressive drugs to generate human tolerogenic DCs with potent immunoregulatory function in vitro (25,26).…”

Section: Conclusion Treatment With Type II Collagenpulsed Tolerogenimentioning

confidence: 99%

Therapeutic effect of tolerogenic dendritic cells in established collagen‐induced arthritis is associated with a reduction in Th17 responses

Stoop¹,

Harry²,

Delwig³

et al. 2010

Arthritis & Rheumatism

123

114

View full text Add to dashboard Cite

Results. Tolerogenic DCs displayed a semimature phenotype, produced low levels of inflammatory cytokines, and exhibited low T cell stimulatory capacity. Upon intravenous injection into arthritic mice, tolerogenic DCs migrated to the spleen, liver, lung, feet, and draining lymph nodes. Treatment of arthritic mice with type II collagen-pulsed tolerogenic DCs, but not unpulsed tolerogenic DCs or mature DCs, significantly inhibited disease severity and progression. This improvement coincided with a significant decrease in the number of Th17 cells and an increase in the number of interleukin-10-producing CD4؉ T cells, whereas tolerogenic DC treatment had no detectable effect on Th1 cells or interleukin-17-producing ␥/␦ T cells.Conclusion. Treatment with type II collagenpulsed tolerogenic DCs decreases the proportion of Th17 cells in arthritic mice and simultaneously reduces the severity and progression of arthritis.

show abstract

Induction of regulatory dendritic cells by dexamethasone and 1α,25-Dihydroxyvitamin D3

Cited by 78 publications

References 45 publications

Dexamethasone Inhibits Maturation and Alters Function of Monocyte-Derived Dendritic Cells from Cord Blood

Dexamethasone Inhibits Maturation and Alters Function of Monocyte-Derived Dendritic Cells from Cord Blood

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

Therapeutic effect of tolerogenic dendritic cells in established collagen‐induced arthritis is associated with a reduction in Th17 responses

Contact Info

Product

Resources

About