| First Author | Park WR | Year | 2004 |
| Journal | Int Immunol | Volume | 16 |
| Issue | 2 | Pages | 295-302 |
| PubMed ID | 14734615 | Mgi Jnum | J:88973 |
| Mgi Id | MGI:3037525 | Doi | 10.1093/intimm/dxh034 |
| Citation | Park WR, et al. (2004) A mechanism underlying STAT4-mediated up-regulation of IFN-gamma induction inTCR-triggered T cells. Int Immunol 16(2):295-302 |
| abstractText | IL-12 promotes T(h)1 development/IFN-gamma expression by activating STAT4. However, it is still unclear how STAT4 elicits IFN-gamma promoter activation. Here, we investigated the mechanism by which IL-12-activated STAT4 functions for IFN-gamma induction in TCR-triggered T cells. TCR stimulation induced high levels of IFN-gamma production depending on co-stimulation with IL-12. IL-12 stimulation greatly enhanced the promoter-binding activity of c-Jun/AP-1, a critical transcription factor for IFN-gamma gene expression in wild-type T cells, but not in STAT4-deficient (STAT4(-/-)) T cells. Comparable amounts of c-Jun were induced by TCR stimulation in both wild-type and STAT4(-/-) T cells irrespective of IL-12 co-stimulation. However, c-Jun bound to STAT4 in IL-12-co-stimulated wild-type T cells. c-Jun forming a complex with STAT4 efficiently interacted with the AP-1-related sequence of the IFN-gamma promoter. Such an enhanced c-Jun binding did not occur in STAT4(-/-) T cells. These results show that STAT4 contributes to enhancing IFN-gamma expression by up-regulating the binding of TCR signal-induced AP-1 to the relevant promoter sequence. |
