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Macrophages Control the Bioavailability of Vitamin D and Vitamin D-Regulated T Cell Responses
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2021-09-21 , DOI: 10.3389/fimmu.2021.722806
Daniel Villalba Lopez 1 , Fatima A H Al-Jaberi 1 , Anders Woetmann 1 , Niels Ødum 1 , Charlotte Menné Bonefeld 1 , Martin Kongsbak-Wismann 1 , Carsten Geisler 1
Affiliation  

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.



中文翻译:

巨噬细胞控制维生素 D 的生物利用度和维生素 D 调节的 T 细胞反应

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。

更新日期:2021-09-21
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