Dynamic expression of transcription factors T-bet and GATA-3 by regulatory T cells maintains immunotolerance

Nat Immunol. 2015 Feb;16(2):197-206. doi: 10.1038/ni.3053. Epub 2014 Dec 15.


Regulatory T cells (Treg cells) can express the transcription factors T-bet and GATA-3, but the function of this expression and whether such cells represent stable subsets is still unknown. By using various reporter tools, we found that the expression of T-bet and GATA-3 in Treg cells was dynamically influenced by the cytokine environment. Treg cell-specific deletion of the gene encoding either T-bet (Tbx21) or GATA-3 (Gata3) alone did not result in loss of Treg cell function; however, mice with combined deficiency in both genes in Treg cells developed severe autoimmune-like diseases. Loss of Treg cell function correlated with upregulation of expression of the transcription factor RORγt and reduced expression of the transcription factor Foxp3. Thus, in the steady state, activated Treg cells transiently upregulated either T-bet or GATA-3 to maintain T cell homeostasis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Autoimmunity
  • Cells, Cultured
  • Colitis / immunology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • GATA3 Transcription Factor / genetics*
  • GATA3 Transcription Factor / metabolism*
  • Gene Expression Regulation*
  • Immune Tolerance / genetics*
  • Mice
  • T-Box Domain Proteins / genetics*
  • T-Box Domain Proteins / metabolism*
  • T-Lymphocytes, Regulatory / immunology*


  • GATA3 Transcription Factor
  • T-Box Domain Proteins
  • T-box transcription factor TBX21