Availability of 25-Hydroxyvitamin D3 to APCs Controls the Balance between Regulatory and Inflammatory T Cell Responses

• Published in: The Journal of immunology (1950) 2012-12, Vol.189 (11), p.5155-5164
• Main Authors: Jeffery, Louisa E., Wood, Alice M., Qureshi, Omar S., Hou, Tie Zheng, Gardner, David, Briggs, Zoe, Kaur, Satdip, Raza, Karim, Sansom, David M.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1200786

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, use 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 show in this study 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 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)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.