Urry, Z;
Chambers, ES;
Xystrakis, E;
Dimeloe, S;
Richards, DF;
Gabryšová, L;
Christensen, J;
... Hawrylowicz, CM; + view all
(2012)
The role of 1α,25-dihydroxyvitamin D3 and cytokines in the promotion of distinct Foxp3 + and IL-10 + CD4 + T cells.
European Journal of Immunology
, 42
(10)
pp. 2697-2708.
10.1002/eji.201242370.
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Abstract
1α,25-Dihydroxyvitamin D3 (1α25VitD3) has potent immunomodulatory properties. We have previously demonstrated that 1α25VitD3 promotes human and murine IL-10-secreting CD4+ T cells. Because of the clinical relevance of this observation, we characterized these cells further and investigated their relationship with Foxp3+ regulatory T (Treg) cells. 1α25VitD3 increased the frequency of both Foxp3+ and IL-10+ CD4+T cells in vitro. However, Foxp3 was increased at high concentrations of 1α25VitD3 and IL-10 at more moderate levels, with little coexpression of these molecules. The Foxp3+ and IL-10+ T-cell populations showed comparable suppressive activity. We demonstrate that the enhancement of Foxp3 expression by 1α25VitD3 is impaired by IL-10. 1α25VitD3 enables the selective expansion of Foxp3+ Treg cells over their Foxp3− T-cell counterparts. Equally, 1α25VitD3 maintains Foxp3+ expression by sorted populations of human and murine Treg cells upon in vitro culture. A positive in vivo correlation between vitamin D status and CD4+Foxp3+ T cells in the airways was observed in a severe pediatric asthma cohort, supporting the in vitro observations. In summary, we provide evidence that 1α25VitD3 enhances the frequency of both IL-10+ and Foxp3+ Treg cells. In a translational setting, these data suggest that 1α25VitD3, over a broad concentration range, will be effective in enhancing the frequency of Treg cells.
| Type: | Article |
|---|---|
| Title: | The role of 1α,25-dihydroxyvitamin D3 and cytokines in the promotion of distinct Foxp3 + and IL-10 + CD4 + T cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/eji.201242370 |
| Publisher version: | http://dx.doi.org/10.1002/eji.201242370 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| 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/1518059 |
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