IκB kinase ε targets interferon regulatory factor 1 in activated T lymphocytes.

I kappa B kinase epsilon (IKK-epsilon) has an essential role as a regulator of innate immunity, functioning downstream of pattern recognition receptors to modulate NF-kappa B and interferon (IFN) signaling. In the present study, we investigated IKK-epsilon activation following T cell receptor (TCR)/CD28 stimulation of primary CD4(+) T cells and its role in the stimulation of a type I IFN response. IKK-epsilon was activated following TCR/CD28 stimulation of primary CD4(+) T cells; however, in T cells treated with poly(I.C), TCR/CD28 costimulation blocked induction of IFN-beta transcription. We demonstrated that IKK-epsilon phosphorylated the transcription factor IFN regulatory factor 1 (IRF-1) at amino acid (aa) 215/219/221 in primary CD4(+) T cells and blocked its transcriptional activity. At the mechanistic level, IRF-1 phosphorylation impaired the physical interaction between IRF-1 and the NF-kappa B RelA subunit and interfered with PCAF-mediated acetylation of NF-kappa B RelA. These results demonstrate that TCR/CD28 stimulation of primary T cells stimulates IKK-epsilon activation, which in turn contributes to suppression of IFN-beta production.