title: Transcriptional regulation of the Th17 immune response by IKK(alpha).
abstract: Th17 cells are a subset of T cells that play crucial roles in the pathogenesis of many inflammatory diseases. We report here the identification of IKKα (inhibitor of NF-κB kinase-α) as a key transcriptional regulator of the Th17 lineage. T cells expressing a nonactivatable form of IKKα were significantly compromised in their ability to produce IL-17 and to initiate neural inflammation. IKKα is present in the nuclei of resting CD4(+) T cells. Upon Th17 differentiation, IKKα selectively associated with the Il17a locus, and promoted its histone H3 phosphorylation and transcriptional activation in a NF-κB-independent manner. These findings indicate that nuclear IKKα maintains the Th17 phenotype by activating the Il17a gene.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Ruan
authors.forename: Brendan
authors.initials: B
authors.lastname: Hilliard
authors.forename: Jennifer
authors.initials: J
authors.lastname: Devirgiliis
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
authors.forename: Youhai H
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control; D051550:I-kappa B Kinase / Q000502:physiology*; D020381:Interleukin-17 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D016328:NF-kappa B / Q000502:physiology; D011401:Promoter Regions, Genetic; D058504:Th17 Cells / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: D020381:Interleukin-17; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016328:NF-kappa B; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase