Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells.
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.
Kimura
Akihiro
A
Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, 1-3, Yamada-oka, Suita, Osaka 565-0871, Japan.
Naka
Tetsuji
T
Nohara
Keiko
K
Fujii-Kuriyama
Yoshiaki
Y
Kishimoto
Tadamitsu
T
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D020381:Interleukin-17 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D020381:Interleukin-17; D015850:Interleukin-6; D018336:Receptors, Aryl Hydrocarbon; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050799:STAT5 Transcription Factor; D016212:Transforming Growth Factor beta