Availability of 25-hydroxyvitamin D(3) to APCs controls the balance between regulatory and inflammatory T cell responses.
Availability of 25-hydroxyvitamin D(3) to APCs controls the balance between regulatory and inflammatory T cell responses.
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DOI：
10.4049/jimmunol.1200786
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发表时间：
2012-12-01
期刊：
影响因子：
--
通讯作者：
Sansom DM
中科院分区：
文献类型：
--
作者：
Jeffery LE;Wood AM;Qureshi OS;Hou TZ;Gardner D;Briggs Z;Kaur S;Raza K;Sansom DM
1,25-二羟基维生素D3 （1,25(OH)2D3）是维生素D的活性形式，对包括免疫系统细胞在内的几种组织产生强有力的影响，影响T细胞的激活、分化和迁移。维生素D的循环无活性形式25(OH)D3通常被用作“维生素D状态”的指示。然而，这种前体的利用取决于细胞对其的摄取，并随后由酶25(OH) d3 -1α-羟化酶（CYP27B1）转化为活性的1,25(OH)2D3。使用人类T细胞，我们现在表明，只有当树突状细胞（dc）存在时，添加失活的25(OH)D3才足以改变T细胞的反应。从机制上讲，CYP27B1在树突细胞成熟时被LPS或T细胞接触诱导，导致125 (OH)2D3的产生和释放，随后影响T细胞的反应。在大多数组织中，维生素D结合蛋白（DBP）作为载体来增强维生素D的利用。然而，我们发现DBP通过限制非活性25(OH)D3对DC的可用性来调节T细胞反应。这些数据表明，dc可用的“游离”25(OH)D3水平决定了随后T细胞反应的炎症/调节平衡。
1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, exerts potent effects on several tissues including cells of the immune system, where it affects T cell activation, differentiation and migration. The circulating, inactive form of vitamin D, 25(OH)D3, is generally used as an indication of “vitamin D status”. However, utilization of this precursor depends on its uptake by cells and subsequent conversion by the enzyme 25(OH)D3-1α-hydroxylase (CYP27B1) into active 1,25(OH)2D3. Using human T cells, we now show that addition of inactive 25(OH)D3 is sufficient to alter T cell responses only when dendritic cells (DCs) are present. Mechanistically, CYP27B1 is induced in DCs upon maturation with LPS or upon T cell contact resulting in the generation and release of 1,25(OH)2D3 which subsequently affects T cell responses. In most tissues, vitamin D binding protein (DBP) acts as a carrier to enhance the utilization of vitamin D. However, we show that DBP modulates T cell responses by restricting the availability of inactive 25(OH)D3 to DC. These data indicate that the level of “free” 25(OH)D3 available to DCs determines the inflammatory/regulatory balance of ensuing T cell responses.
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影响因子：
4.1
作者：
Atkins, Gerald J.;Anderson, Paul H.;Morris, Howard A.
通讯作者：
Morris, Howard A.
DOI：
10.1016/0960-0760(92)90094-y
发表时间：
1992-09-01
影响因子：
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作者：
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DOI：
10.1016/j.jsbmb.2006.12.078
发表时间：
2007-03-01
影响因子：
4.1
作者：
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通讯作者：
Adams, John S.
影响因子：
7
作者：
Hewison, Martin
通讯作者：
Hewison, Martin