Demethylation of TNFSF7 contributes to CD70 overexpression in CD4+ T cells from patients with systemic sclerosis

Clin Immunol. 2012 Apr;143(1):39-44. doi: 10.1016/j.clim.2012.01.005. Epub 2012 Jan 18.

Abstract

The pathogenesis of systemic sclerosis (SSc) is still unclear. CD70, a B cell costimulatory molecule that interacts with CD27 during B-T cell contact, is overexpressed due to demethylation of its promoter regulatory elements in CD4+ T cells from patients with the following autoimmune diseases, namely systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE) and primary Sjögren's syndrome (pSS). However, as an autoimmune disease, it is unknown whether aberrant expression and methylation of CD70 occur in SSc CD4+ T cells. We aimed to investigate whether the aberrant expression and methylation status of CD70 occur in CD4+ T cells from patients with SSc. We found that the CD70 is overexpressed and the CD70 promoter region is demethylated in SSc CD4+ T cells. These findings suggest that demethylation of CD70 promoter region contributes to the overexpression of CD70 in CD4+ T cells and may contribute to autoimmune response in SSc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD27 Ligand / genetics*
  • CD27 Ligand / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • DNA Methylation / genetics*
  • DNA Methylation / immunology
  • Female
  • Gene Expression Regulation / genetics*
  • Gene Expression Regulation / immunology
  • Humans
  • Male
  • Middle Aged
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Scleroderma, Systemic / genetics*
  • Scleroderma, Systemic / immunology
  • Young Adult

Substances

  • CD27 Ligand
  • CD70 protein, human
  • RNA, Messenger