Vitamin D-binding protein controls T cell responses to vitamin D.

Background In vitro studies have shown that the active form of vitamin D₃, 1α,25-dihydroxyvitamin D3 (1,25(OH)₂D₃), can regulate differentiation of CD4⁺ T cells by inhibiting Th1 and Th17 cell differentiation and promoting Th2 and Treg cell differentiation. However, the serum concentration of 1,25(OH)₂D₃ is far below the effective concentration of 1,25(OH)₂D₃ found in in vitro studies, and it has been suggested that 1,25(OH)₂D₃ must be produced locally from the inactive precursor 25-hydroxyvitamin D3 (25(OH)D3) to affect ongoing immune responses in vivo. Although it has been reported that activated T cells express the 25(OH)D- 1α-hydroxylase CYP27B1 that converts 25(OH)D3 to 1,25(OH)₂D₃, it is still controversial whether activated T cells have the capacity to produce sufficient amounts of 1,25(OH)₂D₃ to affect vitamin D-responsive genes. Furthermore, it is not known how the vitamin D-binding protein (DBP) found in high concentrations in serum affects T cell responses to 25(OH)D3. Results We found that activated T cells express CYP27B1 and have the capacity to produce sufficient 1,25(OH)₂D₃ to affect vitamin D-responsive genes when cultured with physiological concentrations of 25(OH)D3 in serum-free medium. However, if the medium was supplemented with serum or purified DBP, DBP strictly inhibited the production of 1,25(OH)₂D₃ and 25(OH)D3-induced T cell responses. In contrast, DBP did not inhibit the effect of exogenous 1,25(OH)₂D₃. Actin, arachidonic acid and albumin did not affect the sequestration of 25(OH)D3 by DBP, whereas carbonylation of DBP did. Conclusions Activated T cells express CYP27B1 and can convert 25(OH)D3 to 1,25(OH)₂D₃ in sufficiently high concentrations to affect vitamin D-responsive genes when cultured in serum-free medium. However, DBP sequesters 25(OH)D3 and inhibits the production of 1,25(OH)₂D₃ in T cells. To fully exploit the immune-regulatory potential of vitamin D, future studies of the mechanisms that enable the immune system to exploit 25(OH)D3 and convert it to 1,25(OH)₂D₃ in vivo are required. [ABSTRACT FROM AUTHOR]