STAT4-mediated transcriptional repression of the IL5 gene in human memory Th2 cells

Sarah R. Gonzales-van Horn, Leonardo D. Estrada, Nicolai S C van Oers, J. David Farrar

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Type I interferon (IFN-α/β) plays a critical role in suppressing viral replication by driving the transcription of hundreds of interferon-sensitive genes (ISGs). While many ISGs are transcriptionally activated by the ISGF3 complex, the significance of other signaling intermediates in IFN-α/β-mediated gene regulation remains elusive, particularly in rare cases of gene silencing. In human Th2 cells, IFN-α/β signaling suppressed IL5 and IL13 mRNA expression during recall responses to T-cell receptor (TCR) activation. This suppression occurred through a rapid reduction in the rate of nascent transcription, independent of de novo expression of ISGs. Further, IFN-α/β-mediated STAT4 activation was required for repressing the human IL5 gene, and disrupting STAT4 dimerization reversed this effect. This is the first demonstration of STAT4 acting as a transcriptional repressor in response to IFN-α/β signaling and highlights the unique activity of this cytokine to acutely block the expression of an inflammatory cytokine in human T cells.

Original languageEnglish (US)
Pages (from-to)1504-1510
Number of pages7
JournalEuropean Journal of Immunology
Volume46
Issue number6
DOIs
StatePublished - Jun 1 2016

Keywords

  • CD4 T cells
  • Cytokines
  • Gene regulation
  • IFNs
  • Transcription factors

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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