The IFN regulatory factor family participates in regulation of Fas ligand gene expression in T cells

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. Fast expression is under the transcriptional regulation of multiple factors, The present study demonstrates that TCR-inducible Fast 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 Fast promoter results in deficient expression of Fast. EMSAs demonstrate specific Fast promoter binding by IRF-1 and IRF-2, Forced expression of either IRF-1 or IRF-2 leads to Fast promoter activation in T cells and Fast expression in heterologous cells. Finally, suppression of IRF-1 expression in T cells results in deficient TCR-induced Fast expression, These results confirm that the IRF family participates in the regulation of FasL gene expression.