T-bet expression is regulated by EGR1-mediated signaling in activated T cells

Hyun Jin Shin, Jee Boong Lee, Sung Hwan Park, Jun Chang, Chang Woo Lee

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

T-bet is a Th1-specific transcription factor that is directly involved in three important pathways for Th1 cell differentiation, namely TCR signaling, and the IFN-γ-STAT1 and IL-12-STAT4 pathways. A recent study also showed that T-bet plays a vital role in innate immunity. However, the molecular mechanism responsible for transcriptional activation of T-bet during T cell development is not yet known. Here, we characterize the essential human T-bet promoter elements and show that binding of EGR1 to this promoter induces T-bet transcription. Notably, overexpression of EGR1 transactivates and, synergistically in concert with TCR signaling, induces T-bet expression in activated T cells. In contrast, depletion of EGR1 significantly decreases T-bet induction. Finally, we report a positive correlation between EGR1 and T-bet expression during T helper cell differentiation. Collectively, these findings provide molecular insight into T-bet transcription and suggest that EGR1 is an upstream regulator of T-bet induction.

Original languageEnglish
Pages (from-to)385-394
Number of pages10
JournalClinical Immunology
Volume131
Issue number3
DOIs
StatePublished - Jun 2009

Keywords

  • EGR1
  • Promoter
  • T helper cells
  • T-bet
  • TCR signaling
  • Transcription

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