Proceedings of the National Academy of Sciences · 2008 · 531 citations · 25 references
Life SciencesImmunologyMolecular BiologyImmunoregulationSignal TransductionTranscriptional RegulationHelper T Cell SubsetsImmune Cell DifferentiationImmune Cell Lineage CommitmentT Cell BiologyT Cell DevelopmentT Cell DifferentiationNaive T CellsSignal Transducer And Activator Of Transcription Signaling In T Cell DifferentiationT Helper 17 DifferentiationT Helper CellsT-helper Cell PolarizationTh17 Cell Differentiation
IL-17-producing T helper cells (Th17) have been recently identified as a previously undescribed subset of helper T cells. Here, we demonstrate that aryl hydrocarbon receptor (Ahr) has an important regulatory function in the commitment of Th17 cells. Ahr was robustly induced under Th17-polarizing conditions. Ahr-deficient naïve T cells showed a considerable loss in the ability to differentiate into Th17 cells when induced by TGF-beta plus IL-6. We were able to demonstrate that Ahr interacts with Stat1 and Stat5, which negatively regulate Th17 development. Whereas Stat1 activation returned to its basal level in Ahr wild type naïve T cells 24 h after stimulation with TGF-beta plus IL-6, Stat1 remained activated in Ahr-deficient naïve T cells after stimulation. These results indicate that Ahr participates in Th17 cell differentiation through regulating Stat1 activation, a finding that constitutes additional mechanisms in the modulation of Th17 cell development.
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IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells
Thomas Korn, Estelle Bettelli, Wenda Gao et al. · Nature · 2007 · 1.8K citations