Eomesodermin promotes interaction of RelA and NFATc2 with the Ifng promoter and multiple conserved noncoding sequences across the Ifng locus in mouse lymphoma BW5147 cells

Small Molecule Inhibitors Targeting Nuclear Factor κB Activation Markedly Reduce Expression of Interleukin-2, but Not Interferon-γ, Induced by Phorbol Esters and Calcium Ionophores

“…The ectopic expression of Eomes confers IFN-γ expression to several types of normal and transformed cells [ 13 , 24 , 42 , 43 , 44 ]. Consistent with these findings, we also reported that the transfection of Eomes promoted IFN-γ expression in mouse lymphoma BW5147 and EL4 cells, neither of which expressed detectable amounts of endogenous Eomes [ 25 , 38 ]. Stimulation with TCR induced Eomes expression in invariant NKT cells [ 37 ].…”

“…The present results demonstrated that TPCA-1 and IKK-16 did not inhibit IFN-γ expression at concentrations that markedly suppressed IL-2 expression in Eomes-transfected EL4 cells stimulated with PMA and IM. We also previously showed that TPCA-1 and IKK-16 moderately reduced IFN-γ expression in Eomes-transfected BW5147 cells [ 38 ]. To generalize these findings, primary T cells were prepared from mouse spleens and used in experiments.…”

“…In addition to T-box sites [ 46 ], the IFN-γ promoter contains binding sites for NF-κB and NFAT [ 47 ]. We previously showed that IFN-γ expression induced by PMA and IM in Eomes-transfected BW5147 cells and EL4 cells was markedly inhibited by FK506 [ 25 , 38 ]. This finding indicated that the calcineurin-NFAT pathway is indispensable for Eomes-dependent IFN-γ expression.…”

“…We recently reported that RelA interacted with the IFN-γ promoter and multiple CNS in Eomes-transfected BW5147 cells [ 38 ]. The dual NF-κB and STAT3 inhibitor, TPCA-1 (2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide) [ 39 , 40 ], moderately reduced IFN-γ expression induced by phorbol 12-myristate 13-acetate (PMA) and ionomycin (IM), whereas RelA binding to the IFN-γ promoter and CNS was more strongly inhibited by TPCA-1 in Eomes-transfected BW5147 cells [ 38 ]. These findings prompted us to verify the necessity of NF-κB for the transcriptional activation of the IFN-γ gene.…”

Interaction between γδTCR signaling and the E protein‐Id axis in γδ T cell development

“…T-bet is a master regulator of Th1 differentiation in all lymphocytes. Eomes has also been implicated in direct regulation of IFNγ, and can promote binding of NFkB and NFAT to the IFNγ promoter 162. Thus, strong γδTCR signaling activates NFkB and NFAT, which directly regulate IFNγ, providing the hallmark effector function of the γδT1 lineage.…”