1alpha,25-dihydroxyvitaminD3 in combination with TGFβ increases the frequency of Foxp3+ Tregs through preferential expansion and usage of IL-2

TY - JOUR

T1 - 1alpha,25-dihydroxyvitaminD3 in combination with TGFβ increases the frequency of Foxp3+ Tregs through preferential expansion and usage of IL-2

AU - Chambers, Emma S

AU - Suwannasaen, Duangchan

AU - Mann, Elizabeth H

AU - Urry, Zoe

AU - Richards, David

AU - Lertmemongkolchai, Ganjana

AU - Hawrylowicz, Catherine M

PY - 2014/9

Y1 - 2014/9

N2 - 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)2 D3), has been shown to increase the frequency of Foxp3+ CD4+ T regulatory cells (Tregs) 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 numbers in humans. The aim of this work was to identify the cytokine milieu required in vitro to promote Foxp3+ Tregs in cultures containing 1,25(OH)2 D3 at more moderate concentrations (10(-7) M). Stimulation of human CD4+ T cells with a combination of 1,25(OH)2 D3 and TGFβ greatly increased the frequency of Foxp3+ Tregs, which is proposed to result from the preferential expansion of Foxp3(+) Tregs, as compared to the Foxp3- Teffector cells, in culture. The differential effect on proliferation may result from enhanced availability and usage of IL-2 by the Foxp3+ Tregs as compared to Foxp3- Teffector cells. In summary, modulation of the cytokine environment to one high in TGFβ in the presence of 1,25(OH)2 D3 (10(-7) M) significantly increased Foxp3+ Treg frequency. This data provides additional evidence for the important immunomodulatory properties of 1,25(OH)2 D3 that exist and may help to control inflammatory diseases.

AB - 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)2 D3), has been shown to increase the frequency of Foxp3+ CD4+ T regulatory cells (Tregs) 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 numbers in humans. The aim of this work was to identify the cytokine milieu required in vitro to promote Foxp3+ Tregs in cultures containing 1,25(OH)2 D3 at more moderate concentrations (10(-7) M). Stimulation of human CD4+ T cells with a combination of 1,25(OH)2 D3 and TGFβ greatly increased the frequency of Foxp3+ Tregs, which is proposed to result from the preferential expansion of Foxp3(+) Tregs, as compared to the Foxp3- Teffector cells, in culture. The differential effect on proliferation may result from enhanced availability and usage of IL-2 by the Foxp3+ Tregs as compared to Foxp3- Teffector cells. In summary, modulation of the cytokine environment to one high in TGFβ in the presence of 1,25(OH)2 D3 (10(-7) M) significantly increased Foxp3+ Treg frequency. This data provides additional evidence for the important immunomodulatory properties of 1,25(OH)2 D3 that exist and may help to control inflammatory diseases.

U2 - 10.1111/imm.12289

DO - 10.1111/imm.12289

M3 - Article

C2 - 24673126

SN - 0019-2805

VL - 143

SP - 52

EP - 60

JO - Immunology

JF - Immunology

IS - 1

ER -