David F Richards

Publications (3)21.11 Total impact

• Article: The role of 1α,25-dihydroxyvitamin D3 and cytokines in the promotion of distinct Foxp3(+) and IL-10(+) CD4(+) T cells.

  Zoë Urry, Emma S Chambers, Emmanuel Xystrakis, Sarah Dimeloe, David F Richards, Leona Gabryšová, Jillian Christensen, Atul Gupta, Sejal Saglani, Andrew Bush, Anne O'Garra, Zarin Brown, Catherine M Hawrylowicz
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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.
  European Journal of Immunology 08/2012; 42(10):2697-708. · 5.10 Impact Factor
• Article: Vitamin D binding protein and asthma severity in children.

  Atul Gupta, Sarah Dimeloe, David F Richards, Andrew Bush, Sejal Saglani, Catherine M Hawrylowicz
  The Journal of allergy and clinical immunology 03/2012; 129(6):1669-71. · 9.17 Impact Factor
• Article: 1α,25-dihydroxyvitamin D3 promotes CD200 expression by human peripheral and airway-resident T cells.

  Sarah Dimeloe, David F Richards, Zoe L Urry, Atul Gupta, Victoria Stratigou, Sophie Farooque, Sejal Saglani, Andrew Bush, Catherine M Hawrylowicz
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  ABSTRACT: CD200, a cell-surface immunoglobulin-like molecule expressed by immune and stromal cells, dampens the pro-inflammatory activity of tissue-resident innate cells via its receptor, CD200R. This interaction appears critical for peripheral immune tolerance, particularly in the airways where excessive inflammation is undesirable. Vitamin D contributes to pulmonary health and promotes regulatory immune pathways, therefore its influence on CD200 and CD200R was investigated. CD200 and CD200R expression were assessed by qPCR and immunoreactivity of human lymphoid, myeloid and epithelial cells following 1α,25-dihydroxyvitamin D3 (1α,25VitD3) exposure in vitro and in peripheral T cells following 1α,25VitD3 oral ingestion in vivo. The effect of 1α25VitD3 was also assessed in human airway-resident cells. 1α25VitD3 potently upregulated CD200 on peripheral human CD4+ T cells in vitro, and in vivo there was a trend towards upregulation in healthy, but not asthmatic individuals. CD200R expression was not modulated in any cells studied. CD200 induction was observed to a lesser extent in CD8+ T cells and not in B cells or airway epithelium. T cells isolated from the human airway also responded strongly to 1α25VitD3 to upregulate CD200. The capacity of 1α,25-dihydroxyvitamin D3 to induce CD200 expression by peripheral and respiratory tract T cells identifies an additional pathway via which vitamin D can restrain inflammation in the airways to maintain respiratory health.
  Thorax 02/2012; 67(7):574-81. · 6.84 Impact Factor