van Etten Evelyne, Decallonne Brigitte, Bouillon Roger, Mathieu Chantal
LEGENDO, Katholieke Universiteit Leuven, O&N niv9, Herestraat 49, 3000 Leuven, Belgium.
J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):457-9. doi: 10.1016/j.jsbmb.2004.03.017.
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.
1,25 - 二羟基维生素D(3)（1,25(OH)(2)D(3)）的免疫效应主要通过树突状细胞（DCs）介导。在体外，1,25(OH)(2)D(3)处理可使小鼠骨髓（BM）来源的DCs更具耐受性，间接改变T淋巴细胞的行为和命运。在体内，用1,25(OH)(2)D(3)或其类似物治疗可预防非肥胖糖尿病（NOD）小鼠患糖尿病。本研究的目的是调查1,25(OH)(2)D(3)类似物TX527对NOD小鼠BM来源的DCs上抗原呈递分子和共刺激/迁移分子表达的影响。在用20 ng/ml粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）+ 20 ng/ml白细胞介素 - 4（8天）培养，随后用1000 ng/ml脂多糖（LPS）+ 100 U/ml干扰素 - γ（2天）培养后，无论有无10(-8)M TX527，对细胞进行计数，并通过荧光激活细胞分选术（FACS）分析CD11c(+) DC群体内主要组织相容性复合体II类分子（MHC II）、CD86、CD40和CD54的表达。经TX527处理后，细胞回收率显著降低，而CD11c(+) DC比例保持不变。在CD11c(+) DCs上，MHC II、CD86和CD54显著下调，CD40上调两倍。总体而言，NOD小鼠BM来源的DCs经TX527处理后变得更具耐受性，证实了1,25(OH)(2)D(3)对小鼠DCs的作用，并可能解释了1,25(OH)(2)D(3)及其类似物对NOD小鼠糖尿病的保护作用。
