Availability of 25-hydroxyvitamin D3 to antigen presenting cells controls the balance between regulatory and inflammatory T cell responses

• Published in: The Journal of immunology (1950) Vol. 189; no. 11; pp. 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: Journal Article
• Language: English
• Published: 19.10.2012
• ISSN: 0022-1767; 1550-6606
• 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, utilization of this precursor depends on its uptake by cells and subsequent conversion by the enzyme 25(OH)D 3 -1α-hydroxylase (CYP27B1) into active 1,25(OH) 2 D 3 . Using human T cells, we now show 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 (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)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.