Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells

Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells
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DOI:
10.4049/jimmunol.164.9.4443
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发表时间:
2000-05-01
影响因子:
4.4
通讯作者:
Di Carlo, V
Di Carlo, V
中科院分区:
医学2区
文献类型:
--
作者:
Piemonti, L;Monti, P;Di Carlo, V

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我们研究了1 α,25-二羟维生素D-3(1 α,25-(OH)(2)D-3)在GM-CSF和IL-4存在下对体外人单核细胞分化的树突状细胞(DC)的分化、成熟和功能的影响。恢复和形态不受高达100 nM的1 α,25-(OH)(2)D-3的影响,在10 nM 1 α,25-(OH)(2)D-3(D-3-DC)存在下分化的DC显示CD 1a表达显著降低,而CD 14保持升高。甘露糖受体和CD 32显著增加,这与内吞活性的增强相关。共刺激分子如CD 40和CD 86轻微降低或无显著影响(CD 80和MHC II)。但经LPS诱导去成熟或与转染CD 40配体的细胞孵育后,D-3-DC的MHC I、MHC II、CD 80、CD 86、CD 40和CD 83表达略有增加,其在经典MLR中的辅助细胞功能也受到抑制。此外,用D-3-DC刺激的同种异体T细胞在第二次MLR中对来自相同或无关供体的未经处理的DC的反应较差,从而表明非特异性低反应性的发作。总之,我们的数据表明,1 α,25-(OH)(2)D-3可以调节免疫系统,通过抑制DC分化和成熟为有效的APC在免疫应答的第一步起作用。
We studied the effects of 1 alpha,25-dihydroxyvitamin D-3 (1 alpha,25-(OH)(2)D-3) on differentiation, maturation, and functions of dendritic cells (DC) differentiated from human monocytes in vitro in the presence of GM-CSF and IL-4 for 7 days. Recovery and morphology were not affected by 1 alpha,25-(OH)(2)D-3 up to 100 nM, DC differentiated in the presence of 10 nM 1 alpha,25-(OH)(2)D-3 (D-3-DC) showed a marked decrease in the expression of CD1a, while CD14 remained elevated. Mannose receptor and CD32 were significantly increased, and this correlated with an enhancement of endocytic activity. Costimulatory molecules such as CD40 and CD86 were slightly decreased or nonsignificantly affected (CD80 and MHC II). However, after induction of De maturation with LPS or incubation with CD40 ligand-transfected cells, D-3-DC showed marginal increases in MHC I, MHC II, CD80, CD86, CD40, and CD83, The accessory cell function of D-3-DC in classical MLR was also inhibited. Moreover, allogeneic T cells stimulated with D-3-DC were poor responders in a second MLR to untreated DC from the same or an unrelated donor, thus indicating the onset of a nonspecific hyporesponsivity. In conclusion, our data suggest that 1 alpha,25-(OH)(2)D-3 may modulate the immune system, acting at the very first step of the immune response through the inhibition of DC differentiation and maturation into potent APC.