title: Unaltered diabetes presentation in NOD mice lacking the vitamin D receptor.
abstract: OBJECTIVE
  Vitamin D deficiency increases risk for type 1 diabetes in genetically predisposed individuals, while high doses of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] prevent insulitis and diabetes in NOD mice.
  
  
  METHODS
  Since 1,25(OH)(2)D(3) regulates gene transcription through the vitamin D receptor (VDR), we investigated the role of VDR in diabetes development by creating NOD mice without functional VDR.
  
  
  RESULTS
  VDR(-/-) NOD mice are rachitic and have lower numbers of putative regulator cells [TCR-alpha/beta(+)CD4(-)CD8(-) (natural killer T-cells) and CD4(+)CD25(+) T-cells [in central and peripheral immune organs compared with VDR(+/+) NOD littermates. Lipopolysaccharide-stimulated VDR(-/-) NOD macrophages expressed lower interleukin (IL)-1, IL-6, and CC chemokine ligand 2 mRNA, correlating with less nuclear translocation of p65 nuclear factor-kappaB compared with VDR(+/+) NOD macrophages. Thymic and lymph node dendritic cells from VDR(-/-) NOD mice displayed an even less mature CD11c(+)CD86(+) phenotype than VDR(+/+) NOD mice. Despite this immune phenotype linked to diabetes in NOD mice, VDR(-/-) NOD mice developed insulitis and diabetes at the same rate and incidence as VDR(+/+) NOD littermates.
  
  
  CONCLUSIONS
  Despite aggravating known immune abnormalities in NOD mice, disruption of VDR does not alter disease presentation in NOD mice in contrast to the more aggressive diabetes presentation in vitamin D-deficient NOD mice.
authors.affiliation: Laboratory of Experimental Medicine and Endocrinology, Department of Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Conny
authors.initials: C
authors.lastname: Gysemans
authors.forename: Evelyne
authors.initials: E
authors.lastname: van Etten
authors.forename: Lutgart
authors.initials: L
authors.lastname: Overbergh
authors.forename: Annapaula
authors.initials: A
authors.lastname: Giulietti
authors.forename: Guy
authors.initials: G
authors.lastname: Eelen
authors.forename: Mark
authors.initials: M
authors.lastname: Waer
authors.forename: Annemieke
authors.initials: A
authors.lastname: Verstuyf
authors.forename: Roger
authors.initials: R
authors.lastname: Bouillon
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D010641:Phenotype; D018167:Receptors, Calcitriol / Q000172:deficiency* / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D018167:Receptors, Calcitriol