Transcriptional regulation of the Th17 immune response by IKK(alpha).

Li Li, Qingguo Ruan, Brendan Hilliard, Jennifer Devirgiliis, Michael Karin, Youhai H Chen

Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

The Journal of experimental medicine 2011 Apr 11

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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.

Citation

Li Li, Qingguo Ruan, Brendan Hilliard, Jennifer Devirgiliis, Michael Karin, Youhai H Chen. Transcriptional regulation of the Th17 immune response by IKK(alpha). The Journal of experimental medicine. 2011 Apr 11;208(4):787-96