Vitamin C enhances the expression of IL17 in a Jmjd2-dependent manner

BMB Rep. 2017 Jan;50(1):49-54. doi: 10.5483/bmbrep.2017.50.1.193.

Abstract

Previously, we reported that vitamin C facilitates the CpG demethylation of Foxp3 enhancer in CD4+Foxp3+ regulatory T cells (Tregs) by enhancing the activity of a DNA demethylase ten-eleven-translocation (Tet). However, it is not clear whether vitamin C affects other helper T cell lineages like T helper type 17 (Th17) cells which are related with Tregs. Here, we show that the expression of interleukin-17A (IL17) increases with the treatment of vitamin C but not with other antioxidants. Interestingly, the upregulation of IL17 was not accompanied by DNA demethylation in Il17 promoter and was independent of Tet enzymes. Rather, vitamin C reduced the trimethylation of histone H3 lysine 9 (H3K9me3) in the regulatory elements of the Il17 locus, and the effects of vitamin C were abrogated by knockdown of jumonji-C domain-containing protein 2 (jmjd2). These results suggest that vitamin C can affect the expression of IL17 by modulating the histone demethylase activity. [BMB Reports 2017; 50(1): 49-54].

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Ascorbic Acid / pharmacology*
  • Cell Line
  • DNA Methylation / drug effects
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dioxygenases
  • Gene Knockdown Techniques
  • Histone Demethylases / deficiency
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism*
  • Histones / metabolism
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Up-Regulation / drug effects

Substances

  • Antioxidants
  • DNA-Binding Proteins
  • Histones
  • Il17a protein, mouse
  • Interleukin-17
  • Proto-Oncogene Proteins
  • Dioxygenases
  • Tet2 protein, mouse
  • Histone Demethylases
  • JMJD2A protein, mouse
  • Ascorbic Acid