Vitamin D regulates cytokine patterns secreted by dendritic cells to promote differentiation of IL-22-producing T cells

PLoS One. 2015 Jun 24;10(6):e0130395. doi: 10.1371/journal.pone.0130395. eCollection 2015.

Abstract

One central mechanism, by which vitamin D regulates human immune responses, is the direct modulation of dendritic cells (DCs). However, the effect of vitamin D on several key DC functions, such as the secretion of central inflammatory cytokines, remains controversial. Moreover, whether vitamin D treatment of DCs regulates their ability to promote differentiation of IL-17-/IL-22-producing T cell subsets, such as Th17 and Th22 cell, is not known. Here, we report that vitamin D treatment during differentiation of monocytes into DCs markedly enhanced their ability to secrete TNF-α, IL-6, IL-1β and IL-23. Cytokines secreted by vitamin D-treated DC were significantly more potent in driving differentiation of IL-22-producing T cells, but not IL-17-producing T cells, as compared to secreted cytokines of not-vitamin D-treated DCs. Finally, we found that the differentiation of IL-22-producing T cells mediated by supernatants of vitamin D-treated DCs was dependent on TNF-α IL-6 and IL-23. In summary, our study suggests a novel role of vitamin D in regulating DC-mediated immune responses in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation*
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Inflammation
  • Interleukin-1beta / metabolism
  • Interleukin-22
  • Interleukin-23 / metabolism
  • Interleukin-6
  • Interleukins / metabolism*
  • Lymphocyte Activation / immunology
  • Monocytes / cytology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism
  • Th17 Cells / cytology
  • Tumor Necrosis Factor-alpha / metabolism
  • Vitamin D / pharmacology*

Substances

  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-23
  • Interleukin-6
  • Interleukins
  • Tumor Necrosis Factor-alpha
  • Vitamin D

Grants and funding

This work was funded by the Ministry of Innovation, Science, Research and Technology of the German State of North Rhine-Westphalia (Grant No. NRW Rückkehrerprogramm, http://www.wissenschaft.nrw.de/), the Center for Molecular Medicine (Grant No. GB4, http://www.zmmk.uni-koeln.de/), and the Deutsche Forschungsgemeinschaft (Grant No. SFB829 - B13; http://www.dfg.de/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.