I kappa B kinase (IKK)-epsilon targets interferon regulatory factor 1 in activated T lymphocytes

IB kinase (IKK-) has an essential role as a regulator of innate immunity, functioning downstream of pattern recognition receptors to modulate NF-B and interferon (IFN) signaling. In the present study, we investigated IKK- 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- 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- transcription. We demonstrated that IKK- 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-B RelA subunit and interfered with PCAF-mediated acetylation of NF-B RelA. These results demonstrate that TCR/CD28 stimulation of primary T cells stimulates IKK- activation, which in turn contributes to suppression of IFN- production.