Laboratory for Experimental Medicine and Endocrinology (LEGENDO), Katholieke Universiteit Leuven (KUL), 3000 Leuven, Belgium.
Diabetes Metab Res Rev. 2011 Nov;27(8):933-41. doi: 10.1002/dmrr.1275.
Differentiation and maturation of dendritic cells yield a cell type with the ability to prime immune responses towards defence and destruction. 1,25(OH)2D3, the active form of vitamin D3, fosters the development of tolerogenic dendritic cells. This study aimed to evaluate the effects of 1,25(OH)2D3 on murine dendritic cell behaviour in vitro and in vivo.
Dendritic cells were differentiated from bone marrow cells of female C57Bl/6 mice in the presence or absence of 10(-8) M 1,25(OH)2D3 for 8 days (IL4 and GM-CSF). Maturation was induced for 48 h (IFNγ, LPS and BALB/C islet homogenate antigen).
Bone marrow-derived dendritic cells displayed a different surface marker profile in the presence of 1,25(OH)2D3 with decreased MHC II, CD86 and CD80 and increased CCR5, DEC205, F4/80 and CD40, as well as lower IL6 and IL12 expression upon LPS/IFNγ stimulation. T-cell proliferation was significantly reduced when exposed to islet antigen-loaded 1,25D3-DCs as compared to control dendritic cells and IL4, IL10, TNFα and TGFβ levels were increased. In vivo, transfer of islet antigen-loaded control dendritic cells resulted in priming of the immune system and hyperacute islet allograft rejection (4/4), whereas this was prevented in 5/7 mice treated with islet antigen-loaded 1,25D3-DCs.
We conclude that in vitro 1,25(OH)2D3 exposure alters dendritic cell behaviour, converting them into a cell type that drives T cells away from destruction towards a regulatory phenotype.
树突状细胞的分化和成熟产生了一种具有激活免疫反应能力的细胞类型，可针对防御和破坏进行免疫。1,25(OH)2D3，维生素 D3 的活性形式，促进了耐受性树突状细胞的发育。本研究旨在评估 1,25(OH)2D3 对体外和体内小鼠树突状细胞行为的影响。
在存在或不存在 10(-8) M 1,25(OH)2D3 的情况下，从雌性 C57Bl/6 小鼠的骨髓细胞中分化树突状细胞 8 天（IL4 和 GM-CSF）。诱导成熟 48 小时（IFNγ、LPS 和 BALB/C 胰岛匀浆抗原）。
骨髓来源的树突状细胞在存在 1,25(OH)2D3 时表现出不同的表面标记物特征，MHC II、CD86 和 CD80 降低，CCR5、DEC205、F4/80 和 CD40 增加，LPS/IFNγ刺激时 IL6 和 IL12 表达降低。与对照树突状细胞和 IL4、IL10、TNFα 和 TGFβ 水平相比，当暴露于负载胰岛抗原的 1,25D3-DC 时，T 细胞增殖显著减少。体内，与对照树突状细胞相比，移植负载胰岛抗原的树突状细胞可引发免疫系统的启动和胰岛同种异体移植物的超急性排斥反应（4/4），而用负载胰岛抗原的 1,25D3-DC 治疗的 5/7 只小鼠则可预防这种情况。
我们得出结论，体外 1,25(OH)2D3 暴露改变了树突状细胞的行为，将其转化为一种可使 T 细胞远离破坏并向调节表型转变的细胞类型。
