DOI: 10.4049/jimmunol.0803217. 1,25-Dihydroxyvitamin D3 and IL-2 Combine to Inhibit T Cell Production of Inflammatory Cytokines and Promote Development of Regulatory T Cells Expressing CTLA-4 and FoxP3

1,25-Dihydroxyvitamin D3 and IL-2 Combine to Inhibit T Cell Production of Inflammatory Cytokines and Promote Development of Regulatory T Cells Expressing CTLA-4 and FoxP3
10.4049/jimmunol.0803217
Crossref journal-article
Oxford University Press (OUP)
The Journal of Immunology (286)
Abstract
Abstract The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has potent immunomodulatory properties that have promoted its potential use in the prevention and treatment of infectious disease and autoimmune conditions. A variety of immune cells, including macrophages, dendritic cells, and activated T cells express the intracellular vitamin D receptor and are responsive to 1,25(OH)2D3. Despite this, how 1,25(OH)2D3 regulates adaptive immunity remains unclear and may involve both direct and indirect effects on the proliferation and function of T cells. To further clarify this issue, we have assessed the effects of 1,25(OH)2D3 on human CD4+CD25− T cells. We observed that stimulation of CD4+CD25− T cells in the presence of 1,25(OH)2D3 inhibited production of proinflammatory cytokines including IFN- γ, IL-17, and IL-21 but did not substantially affect T cell division. In contrast to its inhibitory effects on inflammatory cytokines, 1,25(OH)2D3 stimulated expression of high levels of CTLA-4 as well as FoxP3, the latter requiring the presence of IL-2. T cells treated with 1,25(OH)2D3 could suppress proliferation of normally responsive T cells, indicating that they possessed characteristics of adaptive regulatory T cells. Our results suggest that 1,25(OH)2D3 and IL-2 have direct synergistic effects on activated T cells, acting as potent anti-inflammatory agents and physiologic inducers of adaptive regulatory T cells.
Bibliography
Jeffery, L. E., Burke, F., Mura, M., Zheng, Y., Qureshi, O. S., Hewison, M., Walker, L. S. K., Lammas, D. A., Raza, K., & Sansom, D. M. (2009). 1,25-Dihydroxyvitamin D3 and IL-2 Combine to Inhibit T Cell Production of Inflammatory Cytokines and Promote Development of Regulatory T Cells Expressing CTLA-4 and FoxP3. The Journal of Immunology, 183(9), 5458â5467.
Authors 10
Louisa E. Jeffery (first)
Fiona Burke (additional)
Manuela Mura (additional)
Yong Zheng (additional)
Omar S. Qureshi (additional)
Martin Hewison (additional)
Lucy S. K. Walker (additional)
David A. Lammas (additional)
Karim Raza (additional)
David M. Sansom (additional)
References 67 Referenced 635
Dates
Type	When
Created	15 years, 10 months ago (Oct. 20, 2009, 5:42 p.m.)
Deposited	7 months, 3 weeks ago (Jan. 2, 2025, 11:41 a.m.)
Indexed	3 days, 4 hours ago (Aug. 21, 2025, 1:22 p.m.)
Issued	15 years, 9 months ago (Nov. 1, 2009)
Published	15 years, 9 months ago (Nov. 1, 2009)
Published Print	15 years, 9 months ago (Nov. 1, 2009)
Funders 0
None
BibTeX
@article{Jeffery_2009, title={1,25-Dihydroxyvitamin D3 and IL-2 Combine to Inhibit T Cell Production of Inflammatory Cytokines and Promote Development of Regulatory T Cells Expressing CTLA-4 and FoxP3}, volume={183}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.0803217}, DOI={10.4049/jimmunol.0803217}, number={9}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Jeffery, Louisa E. and Burke, Fiona and Mura, Manuela and Zheng, Yong and Qureshi, Omar S. and Hewison, Martin and Walker, Lucy S. K. and Lammas, David A. and Raza, Karim and Sansom, David M.}, year={2009}, month=nov, pages={5458–5467} }
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  "abstract": "<jats:title>Abstract</jats:title>\n               <jats:p>The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has potent immunomodulatory properties that have promoted its potential use in the prevention and treatment of infectious disease and autoimmune conditions. A variety of immune cells, including macrophages, dendritic cells, and activated T cells express the intracellular vitamin D receptor and are responsive to 1,25(OH)2D3. Despite this, how 1,25(OH)2D3 regulates adaptive immunity remains unclear and may involve both direct and indirect effects on the proliferation and function of T cells. To further clarify this issue, we have assessed the effects of 1,25(OH)2D3 on human CD4+CD25\u2212 T cells. We observed that stimulation of CD4+CD25\u2212 T cells in the presence of 1,25(OH)2D3 inhibited production of proinflammatory cytokines including IFN- \u03b3, IL-17, and IL-21 but did not substantially affect T cell division. In contrast to its inhibitory effects on inflammatory cytokines, 1,25(OH)2D3 stimulated expression of high levels of CTLA-4 as well as FoxP3, the latter requiring the presence of IL-2. T cells treated with 1,25(OH)2D3 could suppress proliferation of normally responsive T cells, indicating that they possessed characteristics of adaptive regulatory T cells. Our results suggest that 1,25(OH)2D3 and IL-2 have direct synergistic effects on activated T cells, acting as potent anti-inflammatory agents and physiologic inducers of adaptive regulatory T cells.</jats:p>",
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