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Diabetes Publish Ahead of Print published online ahead of print October 24, 2007
DOI: 10.2337/db07-1095
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Original Research

UNALTERED DIABETES PRESENTATION IN NOD MICE LACKING THE VITAMIN D RECEPTOR

Conny Gysemans, PhD1, Evelyne van Etten, PhD1, Lutgart Overbergh, PhD1, Annapaula Giulietti, PhD1, Guy Eelen, PhD1, Mark Waer, MD, PhD2, Annemieke Verstuyf, PhD1, Roge Bouillon, MD, PhD1, and Chantal Mathieu, MD, PhD1

1Laboratory of Experimental Medicine and Endocrinology (LEGENDO), Department of Experimental Medicine, Campus Gasthuisberg O&N 1, Katholieke Universiteit Leuven, Leuven, Belgium
22Laboratory of Experimental Transplantation, Department of Experimental Medicine, Campus Gasthuisberg O&N1, Katholieke Universiteit Leuven, Leuven, Belgium

Objective: Vitamin D deficiency increases the risk for type 1 diabetes in genetically-predisposed individuals, while high doses of 1,25-dihydroxyvitamin D3 prevent insulitis and diabetes in NOD mice.

Research Design and Methods: Since 1,25-dihydroxyvitamin D3 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}/ß+CD4-CD8- NKT and CD4+CD25+ T cells) in central and peripheral immune organs compared to VDR +/+ NOD littermates. LPS-stimulated VDR –/– NOD macrophages expressed lower IL-1, IL-6 and CCL2 mRNA, correlating with less nuclear translocation of p65 NF-{kappa}B, compared to 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.

Correspondence: chantal.mathieu{at}med.kuleuven.be

Key Words: immune system • vitamin D • type 1 diabetes • NOD mouse


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