title: IκB kinase ε targets interferon regulatory factor 1 in activated T lymphocytes.
abstract: IκB kinase ε (IKK-ε) has an essential role as a regulator of innate immunity, functioning downstream of pattern recognition receptors to modulate NF-κB and interferon (IFN) signaling. In the present study, we investigated IKK-ε 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-ε 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-β transcription. We demonstrated that IKK-ε 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-κB RelA subunit and interfered with PCAF-mediated acetylation of NF-κB RelA. These results demonstrate that TCR/CD28 stimulation of primary T cells stimulates IKK-ε activation, which in turn contributes to suppression of IFN-β production.
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sgarbanti
authors.forename: Giulia
authors.initials: G
authors.lastname: Marsili
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Remoli
authors.forename: Emilia
authors.initials: E
authors.lastname: Stellacci
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
authors.forename: Dante
authors.initials: D
authors.lastname: Rotili
authors.forename: Edvige
authors.initials: E
authors.lastname: Perrotti
authors.forename: Chiara
authors.initials: C
authors.lastname: Acchioni
authors.forename: Roberto
authors.initials: R
authors.lastname: Orsatti
authors.forename: Nunzio
authors.initials: N
authors.lastname: Iraci
authors.forename: Mathieu
authors.initials: M
authors.lastname: Ferrari
authors.forename: Alessandra
authors.initials: A
authors.lastname: Borsetti
authors.forename: John
authors.initials: J
authors.lastname: Hiscott
authors.forename: Angela
authors.initials: A
authors.lastname: Battistini
mesh_terms: D000107:Acetylation; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics* / Q000378:metabolism; D050856:Interferon Regulatory Factor-1 / Q000235:genetics* / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000235:genetics; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D051550:I-kappa B Kinase; D050856:Interferon Regulatory Factor-1; D016899:Interferon-beta; D051996:Transcription Factor RelA; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C494257:IRF1 protein, human; C498143:RELA protein, human