1,25-dihydroxyvitamin D3 and interleukin-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3
By L. Jeffery, F. Burke, M. Mura, Yong Zheng, O. Qureshi, M. Hewison, L. Walker, D. Lammas, K. Raza, D. Sansom. Journal of Immunology, 2009
658 citations recorded by the source corpus.
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.
Subfields: Endocrinology, Diabetes and Metabolism, Immunology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/26fbf567ecec4b87b35b47b7f49e6e27849171fa
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Citations in the corpus
- Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths (2020, background): “Furthermore, 1,25(OH)2D3 promotes induction of the T regulatory cells, thereby inhibiting inflammatory processes [35].”
- A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection (2020, background): “Vitamin E, as well as vitamin B6, folate, and zinc, maintain the Th1-mediated immune response, while vitamin D inhibits Th1-cell activity [8,94,95].”