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-Juan

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 - 2014

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T-cells
Regulatory T-Lymphocytes
Helper-Inducer T-Lymphocytes
T-Lymphocytes
Chemical activation
Transcription
Gene expression
Cytokines
Gene Expression

Keywords

  • Ikaros
  • NFAT
  • regulatory T cell

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry

Cite this

Regulatory T cells suppress CD4+ T cells through NFAT-dependent transcriptional mechanisms. / Shin, Daniel S.; Jordan, Ayana; Basu, Samik; Thomas, Rajan M.; Bandyopadhyay, Sanmay; De Zoeten, Edwin F.; Wells, Andrew D.; Macian-Juan, Fernando.

In: EMBO Reports, Vol. 15, No. 9, 2014, p. 991-999.

Research output: Contribution to journalArticle

Shin, Daniel S. ; Jordan, Ayana ; Basu, Samik ; Thomas, Rajan M. ; Bandyopadhyay, Sanmay ; De Zoeten, Edwin F. ; Wells, Andrew D. ; Macian-Juan, Fernando. / Regulatory T cells suppress CD4+ T cells through NFAT-dependent transcriptional mechanisms. In: EMBO Reports. 2014 ; Vol. 15, No. 9. pp. 991-999.
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