The active form of vitamin D₃ (1,25(OH)₂D₃) has a great impact on T cell effector function. Thus, 1,25(OH)₂D₃ promotes T helper 2 (Th2) and regulatory T (Treg) cell function and concomitantly inhibits Th1 and Th17 cell function. Thus, it is believed that vitamin D exerts anti-inflammatory effects. However, vitamin D binding protein (DBP) strongly binds both 1,25(OH)₂D₃ and the precursor 25(OH)D₃, leaving only a minor fraction of vitamin D in the free, bioavailable form. Accordingly, DBP in physiological concentrations would be expected to block the effect of vitamin D on T cells and dendritic cells. In the present study, we show that pro-inflammatory, monocyte-derived M1 macrophages express very high levels of the 25(OH)D-1α-hydroxylase CYP27B1 that enables them to convert 25(OH)D₃ into 1,25(OH)₂D₃ even in the presence of physiological concentrations of DBP. Co-cultivation of M1 macrophages with T cells allows them to overcome the sequestering of 25(OH)D₃ by DBP and to produce sufficient levels of 1,25(OH)₂D₃ to affect T cell effector function. This study suggests that in highly inflammatory conditions, M1 macrophages can produce sufficient levels of 1,25(OH)₂D₃ to modify T cell responses and thereby reduce T cell-mediated inflammation via a vitamin D-mediated negative feed-back loop.

维生素 D ₃ (1,25(OH) ₂ D ₃ )的活性形式对 T 细胞效应器功能有很大影响。因此，1,25(OH) ₂ D ₃促进 T 辅助细胞 2 (Th2) 和调节性 T (Treg) 细胞功能，同时抑制 Th1 和 Th17 细胞功能。因此，据信维生素 D 具有抗炎作用。然而，维生素 D 结合蛋白 (DBP) 强烈结合 1,25(OH) ₂ D ₃和前体 25(OH)D ₃，只留下一小部分维生素 D 以游离的、生物可利用的形式存在。因此，生理浓度的 DBP 有望阻断维生素 D 对 T 细胞和树突细胞的影响。在本研究中，我们表明促炎性、单核细胞衍生的 M1 巨噬细胞表达非常高水平的 25(OH)D-1α-羟化酶 CYP27B1，使它们能够将 25(OH)D ₃转化为 1,25(OH) ) ₂ D ₃即使存在生理浓度的 DBP。M1 巨噬细胞与 T 细胞的共培养使它们能够克服DBP对 25(OH)D ₃的隔离并产生足够水平的 1,25(OH) ₂ D ₃影响 T 细胞效应器功能。这项研究表明，在高度炎症条件下，M1 巨噬细胞可以产生足够水平的 1,25(OH) ₂ D ₃来改变 T 细胞反应，从而减少 T 细胞介导的炎症通过 维生素 D 介导的负反馈回路。