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

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• 作者：Evelyne van Etten ; Brigitte Decallonne ; Roger Bouillon ; Chantal Mathieu
• 关键词：Analogs of 1 ; 25(OH)₂D₃ ; Bone marrow-derived dendritic cells ; Diabetes ; NOD mice
• 刊名：The Journal of Steroid Biochemistry and Molecular Biology
• 出版年：2004
• 出版时间：May 2004
• 年：2004
• 卷：89-90
• 期：Complete
• 页码：457-459
• 全文大小：57 K

文摘

The immune effects of 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) are mainly mediated through dendritic cells (DCs). In vitro, 1,25(OH)₂D₃ 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)₂D₃ or its analogs prevents diabetes in NOD mice. The aim of this study was to investigate the effects of the 1,25(OH)₂D₃-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-γ (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)₂D₃ on murine DCs and possibly explaining the protective effects of 1,25(OH)₂D₃ and its analogs from diabetes in NOD mice.