Chambers, ES;
Suwannasaen, D;
Mann, EH;
Urry, Z;
Richards, DF;
Lertmemongkolchai, G;
Hawrylowicz, CM;
(2014)
1 α ,25-dihydroxyvitamin D3 in combination with transforming growth factor- β increases the frequency of Foxp3 + regulatory T cells through preferential expansion and usage of interleukin-2.
Immunology
, 143
(1)
pp. 52-60.
10.1111/imm.12289.
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Abstract
A high prevalence of vitamin D insufficiency and deficiency exists worldwide, which is associated with an increased incidence and severity of a range of immune-mediated diseases. This has resulted in considerable interest in the immunodulatory functions of vitamin D. The active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], has been shown to increase the frequency of Foxp3+ CD4+ T regulatory (Treg) cells when present at high concentrations or under strong T-cell stimulation in culture. Supporting evidence exists in vivo for a positive association between serum 25(OH)D and Foxp3+ Treg cell numbers in humans. The aim of this work was to identify the cytokine milieu required in vitro to promote Foxp3+ Treg cells in cultures containing 1,25(OH)2D3 at more moderate concentrations (10−7 m). Stimulation of human CD4+ T cells with a combination of 1,25(OH)2D3 and transforming growth factor-β (TGF-β) greatly increased the frequency of Foxp3+ Treg cells, which is proposed to result from the preferential expansion of Foxp3+ Treg cells, as compared with the Foxp3− effector T cells, in culture. The differential effect on proliferation may result from enhanced availability and usage of interleukin-2 by the Foxp3+ Treg cells compared with Foxp3− effector T cells. In summary, modulation of the cytokine environment to one high in TGF-β in the presence of 1,25(OH)2D3 (10−7 m) significantly increased Foxp3+ Treg cell frequency. These data provide additional evidence for the important immunomodulatory properties of 1,25(OH)2D3 that exist and may help to control inflammatory diseases.
| Type: | Article |
|---|---|
| Title: | 1 α ,25-dihydroxyvitamin D3 in combination with transforming growth factor- β increases the frequency of Foxp3 + regulatory T cells through preferential expansion and usage of interleukin-2 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/imm.12289 |
| Publisher version: | http://dx.doi.org/10.1111/imm.12289 |
| Language: | English |
| Additional information: | Copyright © 2014 The Authors. Immunology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | 1α,25-dihydroxyvitamin D3; Foxp3+ regulatory T cells; interleukin-2; transforming growth factor-β |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1518053 |
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