Regulatory T cells suppress CD4+ T cells through NFAT-dependent transcriptional mechanisms

EMBO Rep. 2014 Sep;15(9):991-9. doi: 10.15252/embr.201338233. Epub 2014 Jul 29.

Abstract

Regulatory T cells (Tregs) control autoreactive T cells by inhibiting activation-induced proliferation and cytokine expression. The molecular mechanisms responsible for the inactivation of effector T cells by Tregs remain yet to be fully characterized. We report that T-helper cells stimulated in the presence of Tregs quickly activate NFAT1 and have increased NFAT1-dependent expression of the transcription repressor Ikaros. NFAT1 deficiency or dominant-negative Ikaros compromises Treg-mediated inhibition of T-helper cells in vitro and in vivo. Thus, our results place NFAT-dependent mechanisms as general regulators of T-cell tolerance and show that Treg-mediated suppression of T-helper cells results from the activation of NFAT-regulated gene expression.

Keywords: Ikaros; NFAT; regulatory T cell.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cytokines / biosynthesis
  • Gene Expression Regulation
  • Ikaros Transcription Factor / biosynthesis*
  • Ikaros Transcription Factor / genetics
  • Lymphocyte Activation / immunology
  • Mice
  • NFATC Transcription Factors / biosynthesis
  • NFATC Transcription Factors / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Cytokines
  • NFATC Transcription Factors
  • Nfatc2 protein, mouse
  • Zfpn1a1 protein, mouse
  • Ikaros Transcription Factor