Regulatory T Cells-Related Genes Are under DNA Methylation Influence

Int J Mol Sci. 2021 Jul 1;22(13):7144. doi: 10.3390/ijms22137144.

Abstract

Regulatory T cells (Tregs) exert a highly suppressive function in the immune system. Disturbances in their function predispose an individual to autoimmune dysregulation, with a predominance of the pro-inflammatory environment. Besides Foxp3, which is a master regulator of these cells, other genes (e.g., Il2ra, Ctla4, Tnfrsf18, Ikzf2, and Ikzf4) are also involved in Tregs development and function. Multidimensional Tregs suppression is determined by factors that are believed to be crucial in the action of Tregs-related genes. Among them, epigenetic changes, such as DNA methylation, tend to be widely studied over the past few years. DNA methylation acts as a repressive mark, leading to diminished gene expression. Given the role of increased CpG methylation upon Tregs imprinting and functional stability, alterations in the methylation pattern can cause an imbalance in the immune response. Due to the fact that epigenetic changes can be reversible, so-called epigenetic modifiers are broadly used in order to improve Tregs performance. In this review, we place emphasis on the role of DNA methylation of the genes that are key regulators of Tregs function. We also discuss disease settings that have an impact on the methylation status of Tregs and systematize the usefulness of epigenetic drugs as factors able to influence Tregs functions.

Keywords: DNA methylation; Tconv; Tregs; epigenetic modifiers; gene expression.

Publication types

  • Review

MeSH terms

  • CTLA-4 Antigen / genetics
  • DNA Methylation*
  • Epigenesis, Genetic
  • Forkhead Transcription Factors / genetics
  • Gene Expression
  • Gene Expression Regulation
  • Glucocorticoid-Induced TNFR-Related Protein / genetics
  • Humans
  • Ikaros Transcription Factor / genetics
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Lymphocyte Activation / immunology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / physiology*

Substances

  • CTLA-4 Antigen
  • Forkhead Transcription Factors
  • Glucocorticoid-Induced TNFR-Related Protein
  • Interleukin-2 Receptor alpha Subunit
  • Ikaros Transcription Factor