Comparative effect of 25(OH)D3 and 1,25(OH)2D3 on Th17 cell differentiation

Clin Immunol. 2016 May:166-167:59-71. doi: 10.1016/j.clim.2016.02.011. Epub 2016 Apr 1.

Abstract

Vitamin D is a secosteroid hormone that plays an important regulatory role in calcium homeostasis and bone metabolism. Immune cells can both produce and respond to 1,25(OH)2D3. CD4+ T cells from vitamin D receptor (VDR) KO mice produce higher levels of IFN-γ and IL-17 than their wild type counterparts, and play a crucial role in the pathogenesis of autoimmune diseases (AID). We are particularly interested in studying the effect of vitamin D on pathogenic Th17 cells in humans. We investigated the in vitro effect of 1,25(OH)2D3 and 25(OH)D3 on the differentiation and cytokine production of primary CD4+ T cells from normal donors, and cultured in Th17 polarizing conditions. Both forms of vitamin D reduced the expression of pathogenic Th17 markers and their secretion of pro-inflammatory cytokines (IL-17A, IFN-γ). Furthermore, both vitamin D forms induced an expansion of CD25hi cells and upregulated their expression of CTLA-4 and Foxp3 regulatory markers.

Keywords: IL-17A; Th17; Vitamin D.

Publication types

  • Comparative Study

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • CTLA-4 Antigen / metabolism
  • Calcifediol / pharmacology*
  • Calcitriol / pharmacology*
  • Cell Differentiation / drug effects*
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism
  • Gene Expression / drug effects
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-17 / metabolism
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / cytology
  • Th17 Cells / drug effects*
  • Th17 Cells / metabolism
  • Vitamins / pharmacology

Substances

  • CTLA-4 Antigen
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17
  • Receptors, Calcitriol
  • Vitamins
  • Interleukin-10
  • Interferon-gamma
  • Calcitriol
  • Calcifediol