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  • Title: The IFN regulatory factor family participates in regulation of Fas ligand gene expression in T cells.
    Author: Chow WA, Fang JJ, Yee JK.
    Journal: J Immunol; 2000 Apr 01; 164(7):3512-8. PubMed ID: 10725705.
    Abstract:
    TCR engagement leads to the transcriptional activation of cytokine genes and activation-induced cell death. Activated T cells undergo apoptosis upon expression and ligation of Fas ligand (FasL) to Fas/APO-1 (CD95) receptor. FasL expression is under the transcriptional regulation of multiple factors. The present study demonstrates that TCR-inducible FasL expression is also under the direct influence of the IFN regulatory factor (IRF) transcription factor family. Deletion and mutagenesis of a putative IRF-1 binding site in the FasL promoter results in deficient expression of FasL. EMSAs demonstrate specific FasL promoter binding by IRF-1 and IRF-2. Forced expression of either IRF-1 or IRF-2 leads to FasL promoter activation in T cells and FasL expression in heterologous cells. Finally, suppression of IRF-1 expression in T cells results in deficient TCR-induced FasL expression. These results confirm that the IRF family participates in the regulation of FasL gene expression.
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