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

Daniel S. Shin, Ayana Jordan, Samik Basu, Rajan M. Thomas, Sanmay Bandyopadhyay, Edwin F. De Zoeten, Andrew D. Wells, Fernando Macian

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)991-999
Number of pages9
JournalEMBO Reports
Volume15
Issue number9
DOIs
StatePublished - Sep 2014

Keywords

  • Ikaros
  • NFAT
  • regulatory T cell

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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