Griffin M D, Lutz W H, Phan V A, Bachman L A, McKean D J, Kumar R
Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Biochem Biophys Res Commun. 2000 Apr 21;270(3):701-8. doi: 10.1006/bbrc.2000.2490.
We show that the immunosuppressive effects of 1alpha, 25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) are due, in part, to inhibition of the T cell stimulatory functions of dendritic cells (DCs). Addition of 10(-12) and 10(-8) M 1alpha,25(OH)(2)D(3) to murine DC cultures resulted in a concentration-dependent reduction in levels of class II MHC and the co-stimulatory ligands B7-1, B7-2, and CD40 without affecting the number of DCs generated. Higher concentrations of 1alpha,25(OH)(2)D(3) reduced DC yield. The capacity of DCs to induce proliferation of purified allogeneic T cells was reduced by 1alpha,25(OH)(2)D(3). The vitamin D(3) analog, 1alpha,25(OH)(2)-16-ene-23-yne-26,27-hexafluoro-19-nor -D(3), exerted identical effects at 100-fold lower concentrations. Inhibition of DC maturation and stimulatory function was absent in cultures from mice genetically lacking vitamin D receptors (VDR). Vitamin D analogs effectively reduce DC function via VDR-dependent pathways.
我们发现，1α,25-二羟基维生素D3（1α,25(OH)2D3）的免疫抑制作用部分归因于其对树突状细胞（DCs）T细胞刺激功能的抑制。向小鼠DC培养物中添加10^(-12)和10^(-8) M的1α,25(OH)2D3，导致II类MHC以及共刺激配体B7-1、B7-2和CD40水平呈浓度依赖性降低，而不影响产生的DC数量。更高浓度的1α,25(OH)2D3会降低DC产量。1α,25(OH)2D3降低了DC诱导纯化的同种异体T细胞增殖的能力。维生素D3类似物1α,25(OH)2-16-烯-23-炔-26,27-六氟-19-去甲-D3在低100倍的浓度下发挥相同作用。在基因上缺乏维生素D受体（VDR）的小鼠培养物中，未出现DC成熟和刺激功能的抑制。维生素D类似物通过VDR依赖性途径有效降低DC功能。
