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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

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. Green open access

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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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