Downregulation of p53 by Insufficient CTCF in CD4+ T Cells Is an Important Factor Inducing Acute Graft-Versus-Host Disease

Front Immunol. 2020 Sep 29:11:568637. doi: 10.3389/fimmu.2020.568637. eCollection 2020.

Abstract

Recent evidence indicates that p53 plays a protective role against various systemic autoimmune diseases by suppressing pro-inflammatory cytokine production and reducing the number of pathogenic T cells. However, whether abnormal p53 expression participates in the development of acute graft-versus-host disease (aGVHD) remains unclear. In this study, we demonstrated that p53 was downregulated in CD4+ T cells from patients with aGVHD compared with the non-aGVHD group. Furthermore, we confirmed that low expression of CCCTC-binding factor (CTCF) in CD4+ T cells from aGVHD cases is an important factor affecting histone H3K9/K14 hypoacetylation in the p53 promoter and p53 downregulation. Restoring CTCF expression in CD4+ T cells from aGVHD patients increased p53 amounts and corrected the imbalance of Th17 cells/Tregs. Taken together, these results provide novel insights into p53 downregulation in CD4+ T cells from aGVHD patients.

Keywords: CD4+ T cell; CTCF; P300; aGVHD; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CCCTC-Binding Factor / genetics
  • CCCTC-Binding Factor / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Down-Regulation
  • Female
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / immunology*
  • Humans
  • Male
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / immunology*

Substances

  • CCCTC-Binding Factor
  • CTCF protein, human
  • Tumor Suppressor Protein p53