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 language | English |
|---|---|
| Pages (from-to) | 385-394 |
| Number of pages | 10 |
| Journal | Clinical Immunology |
| Volume | 131 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jun 2009 |
Bibliographical note
Funding Information:This study was supported by research grants from the Korea Science and Engineering Foundation through the Rheumatism Research Center (RII-2002-098-05003, 2008) and the Korea Health 21 R&D Project, Ministry of Health and Welfare (03-PJ10-PG13-GD01-0002).
Keywords
- EGR1
- Promoter
- T helper cells
- T-bet
- TCR signaling
- Transcription