Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells

Akihiro Kimura, Tetsuji Naka, Keiko Nohara, Yoshiaki Fujii-Kuriyama, Tadamitsu Kishimoto

Research output: Contribution to journalArticle

336 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)9721-9726
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number28
DOIs
Publication statusPublished - 2008 Jul 15

Fingerprint

Th17 Cells
Aryl Hydrocarbon Receptors
Helper-Inducer T-Lymphocytes
T-Lymphocytes
Interleukin-6
Interleukin-17
Cell Differentiation

Keywords

  • Dioxin receptor
  • IL-17
  • IL-6
  • Regulatory T cells
  • ROR

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells. / Kimura, Akihiro; Naka, Tetsuji; Nohara, Keiko; Fujii-Kuriyama, Yoshiaki; Kishimoto, Tadamitsu.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 28, 15.07.2008, p. 9721-9726.

Research output: Contribution to journalArticle

Kimura, Akihiro ; Naka, Tetsuji ; Nohara, Keiko ; Fujii-Kuriyama, Yoshiaki ; Kishimoto, Tadamitsu. / Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 28. pp. 9721-9726.
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