Regulatory T cell identity: formation and maintenance

Trends Immunol. 2015 Jun;36(6):344-53. doi: 10.1016/ Epub 2015 May 13.


T regulatory (Treg) cells are central to the maintenance of immune homeostasis. The transcription factor forkhead box P3 (Foxp3) is essential for specifying the Treg cell lineage during development, and continued expression of Foxp3 in mature Treg cells is necessary for suppressive function. Loss of Foxp3 expression in Treg cells is associated with autoimmune pathology. Here, we review recent insights into the mechanisms that maintain Treg cell stability and function, and place these findings within the broader understanding of mechanisms that establish Treg cell identity during development. We integrate emerging principles in Treg cell lineage maintenance with the mechanisms that allow Treg cells to sense and respond to varied inflammatory environments, and outline important areas of future inquiry in this context.

Keywords: CpG methylation; DNA looping; Foxp3; TCR; regulatory T cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Lineage / genetics
  • Cell Lineage / immunology*
  • Enhancer Elements, Genetic / genetics
  • Enhancer Elements, Genetic / immunology
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression / immunology
  • Homeostasis / genetics
  • Homeostasis / immunology*
  • Humans
  • Models, Immunological
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism


  • FOXP3 protein, human
  • Forkhead Transcription Factors