Unaltered diabetes presentation in NOD mice lacking the vitamin D receptor.
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.
Gysemans
Conny
C
Laboratory of Experimental Medicine and Endocrinology, Department of Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
van Etten
Evelyne
E
Overbergh
Lutgart
L
Giulietti
Annapaula
A
Eelen
Guy
G
Waer
Mark
M
Verstuyf
Annemieke
A
Bouillon
Roger
R
Mathieu
Chantal
C
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
D018167:Receptors, Calcitriol