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Open Access 01-12-2014 | Research article

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

Authors: Martin Kongsbak, Marina Rode von Essen, Trine Bøegh Levring, Peter Schjerling, Anders Woetmann, Niels Ødum, Charlotte Menné Bonefeld, Carsten Geisler

Published in: BMC Immunology | Issue 1/2014

Abstract

Background

In vitro studies have shown that the active form of vitamin D₃, 1a,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-1a-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)₂D₃in vivo are required.

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Title: Vitamin D-binding protein controls T cell responses to vitamin D
Authors: Martin Kongsbak
Marina Rode von Essen
Trine Bøegh Levring
Peter Schjerling
Anders Woetmann
Niels Ødum
Charlotte Menné Bonefeld
Carsten Geisler
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Immunology / Issue 1/2014
Electronic ISSN: 1471-2172
DOI: https://doi.org/10.1186/s12865-014-0035-2

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

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Conclusions

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