1α, 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. Issue 1 (September 2014)

• Record Type: Journal Article
• Authors: Chambers, Emma S.; Suwannasaen, Duangchan; Mann, Elizabeth H.; Urry, Zoe; Richards, David F.; Lertmemongkolchai, Ganjana; Hawrylowicz, Catherine M.
• Is Part Of: Immunology. Volume 143:Issue 1(2014:Sep.)
• Page Start: 52
• Page End: 60
• Publication Date: 2014-09
• Subjects: Immunology -- Periodicals
• DOI: 10.1111/imm.12289
• Languages: English
• ISSNs: 0019-2805

Abstract

<abstract abstract-type="main" id="imm12289-abs-0001"> <title>Summary</title> <p>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, 1<italic>α</italic>, 25‐dihydroxyvitamin D3 [1, 25(OH)<sub>2</sub>D3], has been shown to increase the frequency of Foxp3<sup>+</sup> CD4<sup>+</sup> T regulatory (Treg) cells when present at high concentrations or under strong T‐cell stimulation in culture. Supporting evidence exists <italic>in vivo</italic> for a positive association between serum 25(OH)D and Foxp3<sup>+</sup> Treg cell numbers in humans. The aim of this work was to identify the cytokine milieu required <italic>in vitro</italic> to promote Foxp3<sup>+</sup> Treg cells in cultures containing 1, 25(OH)<sub>2</sub>D3 at more moderate concentrations (10<sup>−7 </sup><sc>m</sc>). Stimulation of human CD4<sup>+</sup> T cells with a combination of 1, 25(OH)<sub>2</sub>D3 and transforming growth factor‐<italic>β</italic> (TGF‐<italic>β</italic>) greatly increased the frequency of Foxp3<sup>+</sup> Treg cells, which is proposed to result from the preferential expansion of Foxp3<sup>+</sup> Treg cells, as compared with the Foxp3<sup>−</sup> effector T cells, in culture. The differential effect on proliferation may result from enhanced availability and usage of interleukin‐2 by the Foxp3<sup>+</sup> Treg cells compared with Foxp3<sup>−</sup> effector T cells. In summary, modulation of the cytokine environment to one high in TGF‐<italic>β</italic> in the presence of 1, 25(OH)<sub>2</sub>D3 (10<sup>−7</sup> <sc>m</sc>) significantly increased Foxp3<sup>+</sup> Treg cell frequency. These data provide additional evidence for the important immunomodulatory properties of 1, 25(OH)<sub>2</sub>D3 that exist and may help to control inflammatory diseases.</p> </abstract>