Transcriptional and epigenetic regulation of immune tolerance: roles of the NF-κB family members

Cell Mol Immunol. 2019 Apr;16(4):315-323. doi: 10.1038/s41423-019-0202-8. Epub 2019 Mar 12.

Abstract

Immune tolerance is a highly regulated state and involves diverse mechanisms. Central to the induction of tolerance is the targeted modulation of T-cell activities (both effector and regulatory), in which transcription factors play a significant role. The nuclear factor kappa-B (NF-κB) family is a family of transcription factors that not only are critically involved in diverse T-cell responses but also are regulated by many mechanisms to maintain tolerance and T-cell homeostasis. NF-κB, as a transcription factor, has been extensively studied in recent decades, and the molecular mechanisms that regulate NF-κB activities have been well documented. However, recent studies have revealed exciting new roles for NF-κB; in addition to its transcriptional activity, NF-κB can also activate diverse epigenetic mechanisms that mediate extensive chromatin remodeling of target genes to regulate T-cell activities. In this review article, we highlight recent discoveries and emerging opportunities in targeting NF-κB family members as well as their associated chromatin modifiers in the induction of immune tolerance and in the clinical treatment of immune diseases.

Keywords: Immune tolerance; NF-κB; chromatin modifiers.

Publication types

  • Review

MeSH terms

  • Animals
  • Chromatin Assembly and Disassembly
  • Cytokines / metabolism
  • Epigenesis, Genetic* / genetics
  • Epigenesis, Genetic* / immunology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Homeostasis / immunology
  • Humans
  • Immune Tolerance / genetics*
  • Inflammation / genetics*
  • Inflammation / immunology
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • NF-kappa B / physiology
  • Nucleosomes / chemistry
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Transcription Factors / metabolism

Substances

  • Cytokines
  • NF-kappa B
  • Nucleosomes
  • Transcription Factors