TY - JOUR
T1 - Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells
AU - Kimura, Akihiro
AU - Naka, Tetsuji
AU - Nohara, Keiko
AU - Fujii-Kuriyama, Yoshiaki
AU - Kishimoto, Tadamitsu
PY - 2008/7/15
Y1 - 2008/7/15
N2 - 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-β 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-β 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.
AB - 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-β 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-β 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.
KW - Dioxin receptor
KW - IL-17
KW - IL-6
KW - ROR
KW - Regulatory T cells
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UR - http://www.scopus.com/inward/citedby.url?scp=47749107262&partnerID=8YFLogxK
U2 - 10.1073/pnas.0804231105
DO - 10.1073/pnas.0804231105
M3 - Article
C2 - 18607004
AN - SCOPUS:47749107262
SN - 0027-8424
VL - 105
SP - 9721
EP - 9726
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 28
ER -