The Critical Role of Bach2 in Shaping the Balance between CD4+ T Cell Subsets in Immune-Mediated Diseases

Mediators Inflamm. 2019 Dec 30:2019:2609737. doi: 10.1155/2019/2609737. eCollection 2019.

Abstract

The transcription factor Bach2 which is predominantly expressed in B and T lymphocytes represses the expression of genes by forming heterodimers with small Maf and Batf proteins and binding to the corresponding sequence on the DNA. In this way, Bach2 serves as a highly conserved repressor which controls the terminal differentiation and maturation of both B and T lymphocytes. It is required for class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes in activated B cells, and its function in B cell differentiation has been well-described. Furthermore, emerging data show that Bach2 regulates transcriptional activity in T cells at super enhancers or regions of high transcriptional activity, thus stabilizing immunoregulatory capacity and maintaining T cell homeostasis. Bach2 is also critical for the formation and function of CD4+ T cell lineages (Th1, Th2, Th9, Th17, T follicular helper (Tfh), and regulatory T (Treg) cells). Genetic variations within Bach2 locus are associated with numerous immune-mediated diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), chronic pancreatitis (CP), type 2 chronic airway inflammation, inflammatory bowel disease (IBD), and type 1 diabetes. Here, we reveal a critical role of Bach2 in regulating T cell biology and the correlation with these immune-mediated diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology
  • Humans
  • Immune System Diseases / immunology*
  • Immune System Diseases / metabolism*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • BACH2 protein, human
  • Basic-Leucine Zipper Transcription Factors