Availability of 25-Hydroxyvitamin D-3 to APCs Controls the Balance between Regulatory and Inflammatory T Cell Responses

作者：Jeffery Louisa E; Wood Alice M; Qureshi Omar S; Hou Tie Zheng; Gardner David; Briggs Zoe; Kaur Satdip; Raza Karim; Sansom David M^*

来源：The Journal of Immunology, 2012, 189(11): 5155-5164.

DOI：10.4049/jimmunol.1200786

1,25-Dihydroxyvitamin D-3 [1,25(OH)(2)D-3], 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)D-3, is generally used as an indication of vitamin D status. However, use of this precursor depends on its uptake by cells and subsequent conversion by the enzyme 25(OH)D-3-1 alpha-hydroxylase (CYP27B1) into active 1,25(OH)(2)D-3. Using human T cells, we show in this study that addition of inactive 25(OH)D-3 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)(2)D-3, which subsequently affects T cell responses. In most tissues, vitamin D binding protein acts as a carrier to enhance the use of vitamin D. However, we show that vitamin D binding protein modulates T cell responses by restricting the availability of inactive 25(OH)D-3 to DC. These data indicate that the level of free 25(OH)D-3 available to DCs determines the inflammatory/regulatory balance of ensuing T cell responses. The Journal of Immunology, 2012, 189: 5155-5164.

• 出版日期2012-12-1