1,25‐Dihydroxyvitamin D3 inhibits proliferation but not the suppressive function of regulatory T cells in the absence of antigen‐presenting cells

AL Khoo, I Joosten, M Michels, R Woestenenk… - …, 2011 - Wiley Online Library
AL Khoo, I Joosten, M Michels, R Woestenenk, F Preijers, XH He, MG Netea
Immunology, 2011Wiley Online Library
Vitamin D3 is known to induce regulatory T (Treg) cells by rendering antigen‐presenting
cells tolerogenic, its direct effect on human naturally occurring Treg cells is unclear. Here,
we investigated if and how 1, 25‐dihydroxyvitamin D3 [1, 25 (OH) 2D3] can directly affect the
proliferation and function of human naturally occurring Treg cells in vitro. First, we
demonstrated that these Treg cells express vitamin D receptors that were up‐regulated
following anti‐CD3/CD28‐bead stimulation. 1, 25 (OH) 2D3 inhibited proliferation of Treg …
Summary
Vitamin D3 is known to induce regulatory T (Treg) cells by rendering antigen‐presenting cells tolerogenic, its direct effect on human naturally occurring Treg cells is unclear. Here, we investigated if and how 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] can directly affect the proliferation and function of human naturally occurring Treg cells in vitro. First, we demonstrated that these Treg cells express vitamin D receptors that were up‐regulated following anti‐CD3/CD28‐bead stimulation. 1,25(OH)2D3 inhibited proliferation of Treg cells even when exogenous interleukin‐2 was provided. Treg cells were more susceptible to the inhibitory effect of 1,25(OH)2D3 than conventional T cells. 1,25(OH)2D3 neither affected the anergic state nor the suppressive function of Treg cells but induced a subtle increase in interleukin‐10‐secreting cells. The cell‐division‐inhibiting effect of 1,25(OH)2D3 on Treg cells was also demonstrated in vivo by supplementing vitamin D‐deficient HIV‐1‐infected patients with 2000 IU cholecalciferol (vitamin D3). Increased serum 1,25(OH)2D3 levels were associated with a drop in the number and percentage of Treg cells, which may be attributed to a decrease in the proliferating Foxp3+ Treg cell population. In conclusion, 1,25(OH)2D3 directly affects Treg cell growth and promotes interleukin‐10 production without apparent effects on activation status and suppressive phenotype whereas in vivo, high serum 1,25(OH)2D3 levels are associated with reduced Treg cell proliferation and a reduced number of Treg cells.
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