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25-Hydroxy vitamin D3 modulates dendritic cell phenotype and function in Crohn’s disease

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Abstract

Background

In Crohn’s disease (CrD), vitamin D may help to balance an exaggerated immune response and thereby improve the disease course. The immunomodulating effects depend on the activation of 25-hydroxy vitamin D3 (25-D3), into 1,25-dihydroxy vitamin D3 (1,25-D3). This activation has previously been shown to take place in dendritic cells (DC) from healthy individuals. We hypothesised that DC from CrD patients are able to regulate and control inflammatory responses through 25-D3 activation.

Methods

During differentiation, monocyte-derived DC from 20 CrD patients were cultured with either 25-D3 or 1,25-D3 and matured with lipopolysaccharide (LPS). We examined DC surface marker expression, cytokine production, and the ability to induce cell proliferation in an allogeneic mixed leukocyte reaction.

Results

Following stimulation with LPS, DC exposed to either 25-D3 or 1,25-D3 exhibited lower expression levels of CD80, CD83, CD86, and HLA-DR and diminished TNF-α production compared with DC cultured with LPS alone. In contrast, CD14 expression and IL-6 production were higher following 25-D3 or 1,25-D3 treatment. Compared with LPS alone, both forms of vitamin D3 reduced the ability of DC to activate lymphocytes.

Conclusions

Following stimulation with 25-D3, DC from CrD patients displayed a reduced response to LPS with a diminished capability to activate T cells compared with DC stimulated with LPS alone. These data indicate that intrinsic activation of 25-D3 occurs in DC from CrD patients and show that 25-D3 can modulate DC function in CrD. Our data suggest that vitamin D deficiency may contribute to the uncontrolled inflammatory process seen in CrD.

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Abbreviations

25-D3:

25-hydroxy vitamin D3

1,25-D3:

1,25-dihydroxy vitamin D3

CrD:

Crohn’s disease

CD:

Cluster of differentiation

DC:

Dendritic cells

HLA:

Human leucocyte antigen

IFN:

Interferon

IL:

Interleukin

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

LPS:

Lipopolysaccharide

MLR:

Mixed leucocyte reaction

TNF:

Tumour necrosis factor

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Acknowledgments

We thank laboratory technician Rikke Andersen for her excellent laboratory assistance. Financial support: 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 declared.

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Authors and Affiliations

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

    Lars E. Bartels, Søren P. Jørgensen, Mia Bendix, Christian L. Hvas, 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. Søren P. Jørgensen
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  3. Mia Bendix
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  4. Christian L. Hvas
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  5. Jørgen Agnholt
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  7. Jens F. Dahlerup
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Correspondence to Lars E. Bartels.

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Bartels, L.E., Jørgensen, S.P., Bendix, M. et al. 25-Hydroxy vitamin D3 modulates dendritic cell phenotype and function in Crohn’s disease. Inflammopharmacol 21, 177–186 (2013). https://doi.org/10.1007/s10787-012-0168-y

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  • DOI: https://doi.org/10.1007/s10787-012-0168-y

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