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The role of 1α,25-dihydroxyvitamin D3 and cytokines in the promotion of distinct Foxp3 + and IL-10 + CD4 + T cells

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. Green open access

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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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