Transcriptional regulation of the Th17 immune response by IKKα

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 IKK alpha (inhibitor of NF-kappa B kinase-a) as a key transcriptional regulator of the Th17 lineage. T cells expressing a nonactivatable form of IKK alpha were significantly compromised in their ability to produce IL-17 and to initiate neural inflammation. IKK alpha is present in the nuclei of resting CD4(+) T cells. Upon Th17 differentiation, IKK alpha selectively associated with the II17a locus, and promoted its histone H3 phosphorylation and transcriptional activation in a NF-kappa B-independent manner. These findings indicate that nuclear IKK alpha maintains the Th17 phenotype by activating the II17a gene.