NOD bone marrow-derived dendritic cells are modulated by analogs of 1,25-dihydroxyvitamin D3

The immune effects of 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) are mainly mediated through dendritic cells (DCs). In vitro, 1,25(OH)(2)D-3 treatment renders murine bone marrow (BM)-derived DCs more tolerogenic, indirectly altering behavior and fate of T lymphocytes. In vivo, treatment with 1,25(OH)(2)D-3 or its analogs prevents diabetes in NOD mice. The aim of this study was to investigate the effects of the 1,25(OH)(2)D-3-analog TX527 on the expression of antigen-presenting and costimulatory/migratory molecules on BM-derived DCs from NOD mice. After culture with 20 ng/ml GM-CSF + 20 ng/ml IL-4 (8 days) followed by 1000 ng/ml LPS + 100 U/ml IFN-gamma (2 days), with or without 10(-8) M TX527, cells were counted and analyzed by FACS for MHC II, CD86, CD40 and CD54 expression within the CD11c(+) DC population. Upon TX527 treatment, cell recovery was significantly reduced whereas the CD11c(+) DC fraction remained constant. On CD11c(+) DCs, MHC II, CD86 and CD54 were significantly down-regulated and CD40 was twofold upregulated. Globally, BM-derived DCs from NOD mice become more tolerogenic upon TX527 treatment, confirming the effects of 1,25(OH)(2)D-3 on murine DCs and possibly explaining the protective effects of 1,25(OH)(2)D-3 and its analogs from diabetes in NOD mice. (C) 2004 Elsevier Ltd. All rights reserved.