Human dendritic cell antigen presentation and chemotaxis are inhibited by intrinsic 25-hydroxy vitamin D activation

• Published in: International immunopharmacology Vol. 10; no. 8; pp. 922 - 928
• Main Authors: Bartels, Lars E., Hvas, Christian L., Agnholt, Jørgen, Dahlerup, Jens F., Agger, Ralf
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.08.2010; Elsevier
• Subjects: 1-alpha-hydroxylase; 25-hydroxy vitamin D3; Antigen Presentation - drug effects; Antigens, CD - biosynthesis; Antigens, CD - genetics; Antigens, Differentiation - biosynthesis; Antigens, Differentiation - genetics; Biological and medical sciences; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cells, Cultured; Chemokine CCL21 - metabolism; Chemotaxis; Chemotaxis - drug effects; Cholecalciferol; Cholecalciferol - analogs & derivatives; Cholecalciferol - metabolism; Cholecalciferol - pharmacology; Cholestanetriol 26-Monooxygenase - metabolism; Cytokines - biosynthesis; Cytokines - genetics; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Humans; Immunomodulation; Lipopolysaccharides - immunology; Lipopolysaccharides - metabolism; Medical sciences; Monocytes - pathology; Pharmacology. Drug treatments; 25-D3; CC; TT; 1,25-D3; IL; Dendritic cells; VDR; Cholecalciferol; CFSE; TNF; Chemotaxis; LPS; IFN; MFI; APC; GM-CSF; PE; 25-hydroxy vitamin D3; 1-alpha-hydroxylase; DC; Human; Dendritic cell; Antigen presentation; Enzyme; Hydroxylase; Activation; Vitamin D; Antigen presenting cell; Inhibitor; Oxidoreductases; Colecalciferol
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2010.05.003

The immunomodulatory effects of vitamin D have primarily been investigated using the biologically active form 1,25-dihydroxy vitamin D3 (1,25-D3). It was recently demonstrated that dendritic cells (DC) are able to convert the inactive 25-hydroxy vitamin D3 (25-D3) into the active form via 1α-hydroxylase. In this study, we set out to examine the possible consequences of this conversion on adaptive immune functions. Human monocyte-derived DC were matured by lipopolysaccharide (LPS) in the presence or absence of 25-D3. Subsequently, the conversion of 25-D3 into 1,25-D3, and the effects on surface marker expression, cytokine production, antigen-presenting capacity and chemotaxis of the DC were examined. 25-D3 was clearly converted into 1,25-D3 in the DC cultures and the process was accompanied by a reduced expression of CD80 ( p < 0.01), CD83 ( p < 0.01), CD86 ( p = 0.02), and HLA-DR ( p = 0.02). Also, the levels of the pro-inflammatory cytokines tumour necrosis factor (TNF) α ( p = 0.02) and interleukin (IL) 12 ( p < 0.01) were reduced. Interestingly, however, the CD14 expression ( p < 0.01) and the production of IL-1β ( p < 0.01) and IL-6 ( p < 0.01) increased. Thus, 25-D3 affected the delicate interplay between anti- and pro-inflammatory cytokines produced by the DC. Concurrently, 25-D3 reduced DC capacity to induce proliferation of antigen-specific T cells and DC chemotaxis towards chemokine (CC) ligand 21. This indicates that 25-D3 has a regulating function following intrinsic 1α-hydroxylation, a mechanism that potentially has an immunomodulatory effect in vivo.