Transcriptional and epigenetic regulation of T-helper lineage specification

Immunol Rev. 2014 Sep;261(1):62-83. doi: 10.1111/imr.12204.


Combined with TCR stimuli, extracellular cytokine signals initiate the differentiation of naive CD4(+) T cells into specialized effector T-helper (Th) and regulatory T (Treg) cell subsets. The lineage specification and commitment process occurs through the combinatorial action of multiple transcription factors (TFs) and epigenetic mechanisms that drive lineage-specific gene expression programs. In this article, we review recent studies on the transcriptional and epigenetic regulation of distinct Th cell lineages. Moreover, we review current study linking immune disease-associated single-nucleotide polymorphisms with distal regulatory elements and their potential role in the disease etiology.

Keywords: SNPs; STATs; T-helper cell; epigenetic modification; gene regulation; transcription factors.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Enhancer Elements, Genetic / immunology
  • Epigenesis, Genetic / immunology
  • Gene Expression Regulation / immunology
  • Genetic Predisposition to Disease
  • Humans
  • Immune System Diseases / immunology*
  • Polymorphism, Single Nucleotide
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Transcriptional Activation / immunology