title: 1,25-Dihydroxyvitamin D3 alters murine dendritic cell behaviour in vitro and in vivo.
abstract: BACKGROUND
  Differentiation and maturation of dendritic cells yield a cell type with the ability to prime immune responses towards defence and destruction. 1,25(OH)2D3, the active form of vitamin D3, fosters the development of tolerogenic dendritic cells. This study aimed to evaluate the effects of 1,25(OH)2D3 on murine dendritic cell behaviour in vitro and in vivo.
  
  
  METHODS
  Dendritic cells were differentiated from bone marrow cells of female C57Bl/6 mice in the presence or absence of 10(-8) M 1,25(OH)2D3 for 8 days (IL4 and GM-CSF). Maturation was induced for 48 h (IFNγ, LPS and BALB/C islet homogenate antigen).
  
  
  RESULTS
  Bone marrow-derived dendritic cells displayed a different surface marker profile in the presence of 1,25(OH)2D3 with decreased MHC II, CD86 and CD80 and increased CCR5, DEC205, F4/80 and CD40, as well as lower IL6 and IL12 expression upon LPS/IFNγ stimulation. T-cell proliferation was significantly reduced when exposed to islet antigen-loaded 1,25D3-DCs as compared to control dendritic cells and IL4, IL10, TNFα and TGFβ levels were increased. In vivo, transfer of islet antigen-loaded control dendritic cells resulted in priming of the immune system and hyperacute islet allograft rejection (4/4), whereas this was prevented in 5/7 mice treated with islet antigen-loaded 1,25D3-DCs.
  
  
  CONCLUSIONS
  We conclude that in vitro 1,25(OH)2D3 exposure alters dendritic cell behaviour, converting them into a cell type that drives T cells away from destruction towards a regulatory phenotype.
authors: Laboratory for Experimental Medicine and Endocrinology (LEGENDO), Katholieke Universiteit Leuven (KUL), 3000 Leuven, Belgium.
authors: Gabriela Bomfim
authors: GB
authors: Ferreira
authors: Evelyne
authors: E
authors: van Etten
authors: Annemieke
authors: A
authors: Verstuyf
authors: Mark
authors: M
authors: Waer
authors: Lut
authors: L
authors: Overbergh
authors: Conny
authors: C
authors: Gysemans
authors: Chantal
authors: C
authors: Mathieu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D056747:Immunomodulation / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D007515:Islets of Langerhans / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D014184:Transplantation, Homologous
chemical_list: D008070:Lipopolysaccharides; D016753:Interleukin-10; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002117:Calcitriol