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.
Original language | English |
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Pages (from-to) | 2697-708 |
Number of pages | 12 |
Journal | European Journal of Immunology |
Volume | 42 |
Issue number | 10 |
DOIs | |
Publication status | Published - Oct 2012 |
Keywords
- Animals
- Asthma
- CD4 Antigens
- Calcitriol
- Cells, Cultured
- Child
- Cytokines
- Forkhead Transcription Factors
- Humans
- Interleukin-10
- Lymphocyte Activation
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- T-Lymphocyte Subsets
- T-Lymphocytes, Regulatory
- Journal Article
- Research Support, Non-U.S. Gov't