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Oral vitamin D3 supplementation reduces monocyte-derived dendritic cell maturation and cytokine production in Crohn’s disease patients

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Abstract

Background

Low serum vitamin D levels may provoke or aggravate Crohn’s disease (CrD). Vitamin D3 is a well-known immune modulator that affects immune functions in vitro and may prevent CrD flares. Dendritic cells (DC) are key mediators of vitamin D3 effects. In this study, we describe changes in monocyte-derived DC (mo-DC) maturation marker expression and cytokine production following 26 weeks of oral vitamin D3 supplementation in CrD patients.

Methods

Ten CrD patients who had increased serum 25-hydroxy vitamin D levels after oral vitamin D3 and calcium treatment and ten seasonally matched placebo-treated patients were selected for this study. Mo-DC were generated before and after the 26 weeks and induced to mature upon lipopolysaccharide (LPS) stimulation. Maturation marker expression and cytokine production were analysed. Mo-DC function was analysed in a mixed leucocyte reaction (MLR).

Results

Compared with baseline values, LPS-matured mo-DC exhibited reduced expression of CD80 and reduced production of the cytokines IL-10, IL-1β, and IL-6 following 26 weeks of oral vitamin D3 supplementation. Mo-DC performance in an allogeneic MLR was unchanged after vitamin D3 supplementation. Treatment with the placebo did not affect maturation markers, cytokine production, or the MLR.

Conclusions

Vitamin D3 treatment in CrD patients led to hypo-responsive LPS-stimulated mo-DC. This finding indicates that vitamin D3 levels have an impact on the monocytic precursors of mo-DC in vivo and may explain the positive effects of vitamin D3 supplementation on CrD patients. Alternatively, CrD patients with high serum vitamin D3 levels may represent a subgroup with low disease activity.

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Abbreviations

25-D3:

25-Hydroxy vitamin D3

1,25-D3:

1,25-Dihydroxy vitamin D3

25OHD:

Serum 25-hydroxy vitamin D

CFSE:

Carboxyfluorescein succinimidyl ester

CrD:

Crohn’s disease

CDAI:

Crohn’s disease activity index

DC:

Dendritic cell

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

IL:

Interleukin

LPS:

Lipopolysaccharide

MLR:

Mixed leucocyte reaction

mo-DC:

Monocyte-derived dendritic cell

PBMC:

Peripheral blood mononuclear cell

TNF:

Tumour necrosis factor

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Acknowledgments

We thank chief laboratory technician Rikke Andersen for excellent laboratory assistance. The A.P. Møller Foundation for the Advancement of Medical Science, Desiree og Niels Ydes Fond, The Danish Medical Association Research Fund/Højmosegård-Legatet, Aase og Ejnar Danielsens Fond, Karen Elise Jensen Foundation, and the Danish Crohn and Colitis Association supported this study.

Conflict of interest

None.

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Authors and Affiliations

  1. Gastro-Immuno Research Laboratory (GIRL), Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus, Denmark

    Lars E. Bartels, Mia Bendix, Christian L. Hvas, Søren P. Jørgensen, Jørgen Agnholt & Jens F. Dahlerup

  2. Laboratory of Immunology, Aalborg University, Fredrik Bajers Vej 3B, 9220, Aalborg, Denmark

    Lars E. Bartels & Ralf Agger

Authors
  1. Lars E. Bartels
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  2. Mia Bendix
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  3. Christian L. Hvas
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  4. Søren P. Jørgensen
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  5. Jørgen Agnholt
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  6. Ralf Agger
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  7. Jens F. Dahlerup
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Correspondence to Lars E. Bartels.

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Bartels, L.E., Bendix, M., Hvas, C.L. et al. Oral vitamin D3 supplementation reduces monocyte-derived dendritic cell maturation and cytokine production in Crohn’s disease patients. Inflammopharmacol 22, 95–103 (2014). https://doi.org/10.1007/s10787-013-0197-1

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  • DOI: https://doi.org/10.1007/s10787-013-0197-1

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