title: TGF-β-induced IκB-ζ controls Foxp3 gene expression.
abstract: Inhibitor of kappa B (IκB)-ζ, a member of the nuclear IκB family of proteins, is induced by the transforming growth factor (TGF)-β signaling pathway and plays a pivotal role in maintaining the balance of T helper (Th) cell subsets. IκB-ζ deficiency results in reduced percentages of Th17 cells and increased percentages of Th1 cells. In this study, the effects of IκB-ζ deficiency on T-cell subsets were examined further. The data showed that IκB-ζ-deficient T cells had a high capacity for generation of regulatory T cells (Tregs) when T cells were cultured under TGF-β stimulation in the presence of cytokine-neutralizing antibodies. Mechanistically, IκB-ζ itself negatively regulated activation of the Foxp3 promoter in a nuclear factor of kappaB-dependent manner. Thus, this study showed that IκB-ζ controlled Treg differentiation.
authors.affiliation: Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan; School of Medicine, Gifu University, Gifu 501-1194, Japan. Electronic address: ta-maru@umin.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: MaruYama
mesh_terms: D045744:Cell Line, Tumor; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000096:biosynthesis / Q000502:physiology*; D011401:Promoter Regions, Genetic; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016212:Transforming Growth Factor beta; D051550:I-kappa B Kinase
keywords: Foxp3; Gene regulation; Inhibitor of kappaB-ζ