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

Int Immunopharmacol. 2010 Aug;10(8):922-8. doi: 10.1016/j.intimp.2010.05.003. Epub 2010 May 17.


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 1 alpha-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) alpha (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-1 beta (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 1 alpha-hydroxylation, a mechanism that potentially has an immunomodulatory effect in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / drug effects
  • Antigens, CD / biosynthesis*
  • Antigens, CD / genetics
  • Antigens, Differentiation / biosynthesis*
  • Antigens, Differentiation / genetics
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Chemokine CCL21 / metabolism
  • Chemotaxis / drug effects
  • Cholecalciferol / analogs & derivatives
  • Cholecalciferol / metabolism
  • Cholecalciferol / pharmacology*
  • Cholestanetriol 26-Monooxygenase / metabolism*
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Humans
  • Immunomodulation
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / metabolism
  • Monocytes / pathology


  • Antigens, CD
  • Antigens, Differentiation
  • Chemokine CCL21
  • Cytokines
  • Lipopolysaccharides
  • Cholecalciferol
  • Cholestanetriol 26-Monooxygenase