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High-dose cholecalciferol supplementation significantly increases peripheral CD4+ Tregs in healthy adults without negatively affecting the frequency of other immune cells

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Abstract

Background

Regulatory T cells (Tregs) play a central role in the maintenance of self-tolerance. Animal and in vitro studies suggest that vitamin D is involved in reducing the risk of autoimmunity by modulating Tregs.

Methods

In a double-blind, placebo controlled study in 60 healthy volunteers, we assessed the effect of a 12-week high-dose oral cholecalciferol supplementation (140,000 IU/month) on the number and function of CD4posCD25highFoxP3posCD127dim Tregs. We also assessed the clinical safety of the supplementation and the effect on the frequency of other immune cells such as monocytes, dendritic cells, natural killer cells, natural killer T cells, B cells and subgroups of T cells. We also tested the in vitro effect of cholecalciferol on Tregs in human cell cultures.

Results

By using FACS analysis, ex vivo suppressive co-cultures and apoptosis assays, we were able to show that a cholecalciferol supplementation leads to significantly increased numbers of peripheral Tregs in vivo. Tregs function and the frequency of other immune cells remained unchanged, and no clinically relevant safety concerns were found. The in vitro exposure of human peripheral blood mononuclear cells to cholecalciferol also supported our in vivo findings.

Conclusions

Our results indicate a substantial effect of a supplementation with inactive vitamin D on the immune system of healthy humans in vivo and provide a rationale for future studies to investigate the immunomodulatory effects of vitamin D in autoimmune diseases.

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Notes

  1. When the term vitamin D is used without a subscript it always refers to the total of vitamin D2 and vitamin D3. This is also the case for any vitamin D metabolites.

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Acknowledgments

The authors would like to thank N. Hütter for help with recruiting study participants and S. Mautner for help with the manuscript. This work was supported by FFG Austria, BioPersMed (COMET K-project 825329).

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Correspondence to Thomas R. Pieber.

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Prietl, B., Treiber, G., Mader, J.K. et al. High-dose cholecalciferol supplementation significantly increases peripheral CD4+ Tregs in healthy adults without negatively affecting the frequency of other immune cells. Eur J Nutr 53, 751–759 (2014). https://doi.org/10.1007/s00394-013-0579-6

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