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

Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9721-6. doi: 10.1073/pnas.0804231105. Epub 2008 Jul 7.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Interleukin-17 / biosynthesis*
  • Interleukin-6 / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / physiology*
  • STAT1 Transcription Factor / metabolism*
  • STAT5 Transcription Factor / metabolism
  • T-Lymphocytes, Helper-Inducer / cytology*
  • Transforming Growth Factor beta / pharmacology

Substances

  • Interleukin-17
  • Interleukin-6
  • Receptors, Aryl Hydrocarbon
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT5 Transcription Factor
  • Transforming Growth Factor beta