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

Research output: Contribution to journalArticlepeer-review

Authors

  • Zoë Urry
  • Emma S Chambers
  • Emmanuel Xystrakis
  • Leona Gabryšová
  • Jillian Christensen
  • Atul Gupta
  • Sejal Saglani
  • Andrew Bush
  • Anne O'Garra
  • Zarin Brown
  • Catherine M Hawrylowicz

External organisations

  • King's College London

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.

Details

Original languageEnglish
Pages (from-to)2697-708
Number of pages12
JournalEuropean Journal of Immunology
Volume42
Issue number10
Publication statusPublished - 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