Sa.104. The Effects of TX527, a 1,25-Dihydroxyvitamin D3 Analogue, on Human Dendritic Cells: A Proteomic Approach

Abstract25-Hydroxyvitamin D3-1α-hydroxylase (25(OH)D3-1α-hydroxylase), the key enzyme of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) production, is expressed in monocyte-derived macrophages (MACs). Here we show for the first time constitutive expression of 25(OH)D3-1α-hydroxylase in monocyte-derived dendritic cells (DCs), which was increased after stimulation with lipopolysaccharide (LPS). Accordingly, DCs showed low constitutive production of 1,25(OH)2D3, but activation by LPS increased 1,25(OH)2D3 synthesis. In addition, 25(OH)D3-1α-hydroxylase expression was found in blood DCs but not in CD34+-derived DCs. Next we analyzed the functional consequences of these results. Addition of 1,25(OH)2D3 at concentrations comparable with those produced by DCs inhibited the allostimulatory potential of DCs during the early phase of DC differentiation. However, terminal differentiation decreased the responsiveness of DCs to 1,25(OH)2D3. In conclusion, DCs are able to produce 1,25(OH)2D3 especially following stimulation with LPS. Terminal maturation renders DCs unresponsive to the effects of 1,25(OH)2D3, but those cells are able to suppress the differentiation of their own precursor cells in a paracrine way through the production of 1,25(OH)2D3.

Download Full-text

1,25-Dihydroxyvitamin D3 modulates the phenotype and function of Monocyte derived dendritic cells in cattle

BMC Veterinary Research ◽

10.1186/s12917-017-1309-8 ◽

2017 ◽

Vol 13 (1) ◽

Cited By ~ 5

Author(s):

Yolanda Corripio-Miyar ◽

Richard J. Mellanby ◽

Katy Morrison ◽

Tom N. McNeilly

Keyword(s):

Dendritic Cells ◽

Dihydroxyvitamin D3 ◽

1,25 Dihydroxyvitamin D3 ◽

And Function

Download Full-text

1,25-Dihydroxyvitamin D3-Conditioned CD11c+ Dendritic Cells are Effective Initiators of CNS Autoimmune Disease

Frontiers in Immunology ◽

10.3389/fimmu.2015.00575 ◽

2015 ◽

Vol 6 ◽

Cited By ~ 13

Author(s):

Dario Besusso ◽

Louise Saul ◽

Melanie D. Leech ◽

Richard A. O’Connor ◽

Andrew S. MacDonald ◽

...

Keyword(s):

Dendritic Cells ◽

Autoimmune Disease ◽

Dihydroxyvitamin D3 ◽

1,25 Dihydroxyvitamin D3

Download Full-text

Expression of the inhibitory receptor ILT3 on dendritic cells is dispensable for induction of CD4+Foxp3+ regulatory T cells by 1,25-dihydroxyvitamin D3

Blood ◽

10.1182/blood-2005-05-2044 ◽

2005 ◽

Vol 106 (10) ◽

pp. 3490-3497 ◽

Cited By ~ 263

Author(s):

Giuseppe Penna ◽

Andrea Roncari ◽

Susana Amuchastegui ◽

Kenn C. Daniel ◽

Emilio Berti ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Regulatory T Cells ◽

T Cell Activation ◽

Cell Activation ◽

Interferon Γ ◽

Dihydroxyvitamin D3 ◽

1,25 Dihydroxyvitamin D3 ◽

Plasmacytoid Dcs

Abstract1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a secosteroid hormone that renders dendritic cells (DCs) tolerogenic, favoring the induction of regulatory T cells. Induction of DCs with tolerogenic properties by 1,25(OH)2D3 is associated with increased selective expression of immunoglobulin-like transcript 3 (ILT3), suggesting its involvement in the immunoregulatory properties of this hormone. Here we show an in vivo correlate of the increased ILT3 expression on DCs in healing psoriatic lesions following topical treatment with the 1,25(OH)2D3 analog calcipotriol. Analysis of DC subsets reveals a differential regulation of ILT3 expression by 1,25(OH)2D3, with a marked up-regulation in myeloid DCs but no effect on its expression by plasmacytoid DCs. A regulatory role for ILT3 expressed on DCs is indicated by the increased interferon-γ (IFN-γ) secretion promoted by anti-ILT3 addition to cultures of DCs and T cells, but this effect is blunted in 1,25(OH)2D3-treated DCs, suggesting ILT3-independent mechanisms able to regulate T-cell activation. Although ILT3 expression by DCs is required for induction of regulatory T cells, DC pretreatment with 1,25(OH)2D3 leads to induction of CD4+Foxp3+ cells with suppressive activity irrespective of the presence of neutralizing anti-ILT3 monoclonal antibody (mAb), indicating that ILT3 expression is dispensable for the capacity of 1,25(OH)2D3-treated DCs to induce regulatory T cells.

Download Full-text