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

Gorman, Shelley; Judge, Melinda A.; Hart, Prue H.

doi:10.1038/jid.2010.167

Cited by 16 publications

(13 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…RNA was purified from 10 5 purified CD11c+ cells, cDNA transcribed and real-time PCR performed as described previously [41], using a Dendritic Cell and Antigen-Presenting Cell RT 2 profiler PCR array (PAM406Z, 96-wells) to detect gene expression of CCL5, CCL11, CCL19, CCL20, CXCL1 and IL-18RA as described by the manufacturer (Qiagen, Doncaster, VIC, Australia). Fold-change was determined by using the 2 −ΔΔCt method specified by the manufacturer by combining results obtained for multiple house-keeping genes.…”

Section: Methodsmentioning

confidence: 99%

Reversible Control by Vitamin D of Granulocytes and Bacteria in the Lungs of Mice: An Ovalbumin-Induced Model of Allergic Airway Disease

et al. 2013

Self Cite

View full text Add to dashboard Cite

Vitamin D may be essential for restricting the development and severity of allergic diseases and asthma, but a direct causal link between vitamin D deficiency and asthma has yet to be established. We have developed a ‘low dose’ model of allergic airway disease induced by intraperitoneal injection with ovalbumin (1 µg) and aluminium hydroxide (0.2 mg) in which characteristics of atopic asthma are recapitulated, including airway hyperresponsiveness, antigen-specific immunoglobulin type-E and lung inflammation. We assessed the effects of vitamin D deficiency throughout life (from conception until adulthood) on the severity of ovalbumin-induced allergic airway disease in vitamin D-replete and -deficient BALB/c mice using this model. Vitamin D had protective effects such that deficiency significantly enhanced eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male but not female mice. Vitamin D also suppressed the proliferation and T helper cell type-2 cytokine-secreting capacity of airway-draining lymph node cells from both male and female mice. Supplementation of initially vitamin D-deficient mice with vitamin D for four weeks returned serum 25-hydroxyvitamin D to levels observed in initially vitamin D-replete mice, and also suppressed eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male mice. Using generic 16 S rRNA primers, increased bacterial levels were detected in the lungs of initially vitamin D-deficient male mice, which were also reduced by vitamin D supplementation. These results indicate that vitamin D controls granulocyte levels in the bronchoalveolar lavage fluid in an allergen-sensitive manner, and may contribute towards the severity of asthma in a gender-specific fashion through regulation of respiratory bacteria.

show abstract

Section: Methodsmentioning

confidence: 99%

Reversible Control by Vitamin D of Granulocytes and Bacteria in the Lungs of Mice: An Ovalbumin-Induced Model of Allergic Airway Disease

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…21,22 1,25(OH) 2 D 3 can also act directly on CD4 + CD25 ) T cells to generate Foxp3 + T cells expressing high levels of cytotoxic T-lymphocyte antigen-4 that are capable of immune suppression. 23 In mouse models, 1,25(OH) 2 D 3 enhanced the proliferative capacity of CD4 + CD25 + Treg cells 24 and their ability to suppress T helper type 2 (Th2) activity. 25 However, there is limited information on the direct effects of 1,25(OH) 2 D 3 on human naturally occurring Treg cells.…”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

“…Vitamin D 3 interferes with the maturation and differentiation of dendritic cells and may induce a so-called tolerogenic phenotype. 19,20 24 and their ability to suppress T helper type 2 (Th2) activity. 25 However, there is limited information on the direct effects of 1,25(OH) 2 D 3 on human naturally occurring Treg cells.…”

Section: Introductionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3 inhibits proliferation but not the suppressive function of regulatory T cells in the absence of antigen-presenting cells

et al. 2011

View full text Add to dashboard Cite

Summary Vitamin D3 is known to induce regulatory T (Treg) cells by rendering antigen‐presenting cells tolerogenic, its direct effect on human naturally occurring Treg cells is unclear. Here, we investigated if and how 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] can directly affect the proliferation and function of human naturally occurring Treg cells in vitro. First, we demonstrated that these Treg cells express vitamin D receptors that were up‐regulated following anti‐CD3/CD28‐bead stimulation. 1,25(OH)2D3 inhibited proliferation of Treg cells even when exogenous interleukin‐2 was provided. Treg cells were more susceptible to the inhibitory effect of 1,25(OH)2D3 than conventional T cells. 1,25(OH)2D3 neither affected the anergic state nor the suppressive function of Treg cells but induced a subtle increase in interleukin‐10‐secreting cells. The cell‐division‐inhibiting effect of 1,25(OH)2D3 on Treg cells was also demonstrated in vivo by supplementing vitamin D‐deficient HIV‐1‐infected patients with 2000 IU cholecalciferol (vitamin D3). Increased serum 1,25(OH)2D3 levels were associated with a drop in the number and percentage of Treg cells, which may be attributed to a decrease in the proliferating Foxp3+ Treg cell population. In conclusion, 1,25(OH)2D3 directly affects Treg cell growth and promotes interleukin‐10 production without apparent effects on activation status and suppressive phenotype whereas in vivo, high serum 1,25(OH)2D3 levels are associated with reduced Treg cell proliferation and a reduced number of Treg cells.

show abstract

“…Transcript concentrations were determined using standard curves. Relative fold changes in gene expression between BM‐derived DCs from non‐irradiated and UV‐irradiated mice were determined using the 2 −∆∆Ct normalization method …”

Section: Methodsmentioning

confidence: 99%

Characterization of regulatory dendritic cells differentiated from the bone marrow of UV‐irradiated mice

Scott

Bisley

et al. 2013

Immunology

Self Cite

View full text Add to dashboard Cite

SummaryWhen antigen-loaded dendritic cells (DCs) differentiated from the bone marrow (BM) of UV-irradiated mice (UV-BMDCs) were adoptively transferred into naive mice or mice pre-sensitized with that antigen, the recipients exhibited a reduced immune response following antigen challenge. Hence, UV-BMDCs are poorly immunogenic and can suppress pre-existing immunity. The UV-induced effect on BM-derived DCs was rapid (observed 1 day after UV radiation), long-lasting (observed 10 days after UV radiation) and UV dose-dependent. The mechanism by which UV-BMDCs could regulate immunity was investigated. The CD11c + cells, differentiated using granulocyte-macrophage colony-stimulating factor + interleukin-4, were confirmed to be DCs because they did not express the myeloid-derived suppressor cell marker, Gr1. UV-BMDCs did not display altered antigen uptake, processing or ability to activate T cells in vitro. When gene expression in UV-BMDCs and DCs differentiated from the BM of non-irradiated mice (control-BMDCs) was examined, Ccl7, Ccl8 and CSF1R (CD115) mRNA transcripts were up-regulated in UV-BMDCs compared with control-BMDCs. However, neutralizing antibodies for Ccl7 and Ccl8 did not abrogate the reduced immunogenicity of UV-BMDCs in vivo. Moreover, the up-regulation of CSF1R transcript did not correspond with increased receptor expression on UV-BMDCs. The phenotypes of UV-BMDCs and control-BMDCs were similar, with no difference in the expression of CD4, CD8a, CD103, B220 or F4/80, or the regulatory molecules CCR7 (CD197), FasL (CD95L), B7H3 (CD276) and B7H4. However, PDL1 (CD274) expression was reduced in UV-BMDCs compared with control-BMDCs following lipopolysaccharide stimulation. In summary, UV-BMDCs do not express the classical phenotypic or gene expression properties of DCs reported by others as 'regulatory' or 'tolerogenic'.

show abstract

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

Cited by 16 publications

References 36 publications

Reversible Control by Vitamin D of Granulocytes and Bacteria in the Lungs of Mice: An Ovalbumin-Induced Model of Allergic Airway Disease

Reversible Control by Vitamin D of Granulocytes and Bacteria in the Lungs of Mice: An Ovalbumin-Induced Model of Allergic Airway Disease

1,25-Dihydroxyvitamin D3 inhibits proliferation but not the suppressive function of regulatory T cells in the absence of antigen-presenting cells

Characterization of regulatory dendritic cells differentiated from the bone marrow of UV‐irradiated mice

Contact Info

Product

Resources

About