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01-04-2014 | Original Contribution

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

Authors: Barbara Prietl, Gerlies Treiber, Julia K. Mader, Evelyne Hoeller, Michael Wolf, Stefan Pilz, Winfried B. Graninger, Barbara M. Obermayer-Pietsch, Thomas R. Pieber

Published in: European Journal of Nutrition | Issue 3/2014

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 CD4^posCD25^highFoxP3^posCD127^dim 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.

Available only for authorised users

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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Title: High-dose cholecalciferol supplementation significantly increases peripheral CD4+ Tregs in healthy adults without negatively affecting the frequency of other immune cells
Authors: Barbara Prietl
Gerlies Treiber
Julia K. Mader
Evelyne Hoeller
Michael Wolf
Stefan Pilz
Winfried B. Graninger
Barbara M. Obermayer-Pietsch
Thomas R. Pieber
Publication date: 01-04-2014
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nutrition / Issue 3/2014
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-013-0579-6

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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

Abstract

Background

Methods

Results

Conclusions

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Abstract

Background

Methods

Results

Conclusions

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