1,25-Dihydroxyvitamin D3 Alters the Profile of Bone Marrow-Derived Dendritic Cells of NOD Mice

doi:10.1196/annals.1337.030

Address for correspondence: C. Mathieu, Laboratorium voor Experimentele Geneeskunde en Endocrinologie (LEGENDO), Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium. Voice: +32-16-345970; fax: +32-16-345934. chantal.mathieu{at}med.kuleuven.ac.be

1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] prevents autoimmune diabetesin nonobese diabetic (NOD) mice. A major target for 1,25(OH)₂D₃in the immune system is the dendritic cell (DC). Since importantDC abnormalities have been described in NOD mice, we investigatedthe effects of 1,25(OH)₂D₃ on the yield and phenotype of DCsgenerated from bone marrow of NOD mice compared to control congenicnonobese diabetes-resistant (NOR) mice. In both mouse strains,exposure of the bone marrow-derived cells to 1,25(OH)₂D₃ increasedthe proportion of CD11c⁺ DCs after culture. Surface expressionof MHC II, CD86, and CD54 on NOR-derived DCs was decreased after1,25(OH)₂D₃ treatment, while CD40 remained unchanged. On NOD-derivedDCs, 1,25(OH)₂D₃ only inhibited the expression of MHC II andCD86. 1,25(OH)₂D₃ inhibited IL-12 and IL-10 secretion afterIFN ${gamma}$ and LPS stimulation. In vitro treatment with 1,25(OH)₂D₃alters DC yield from bone marrow cultures and alters the phenotypeof the cells in NOD as well as in NOR mice. NOD-derived DCswere more resistant to the 1,25(OH)₂D₃ effects than were NOR-derivedDCs.