The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins

Nature. 2008 May 1;453(7191):106-9. doi: 10.1038/nature06881. Epub 2008 Mar 23.


The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor best known for mediating the toxicity of dioxin. Environmental factors are believed to contribute to the increased prevalence of autoimmune diseases, many of which are due to the activity of T(H)17 T cells, a new helper T-cell subset characterized by the production of the cytokine IL-17. Here we show that in the CD4+ T-cell lineage of mice AHR expression is restricted to the T(H)17 cell subset and its ligation results in the production of the T(H)17 cytokine interleukin (IL)-22. AHR is also expressed in human T(H)17 cells. Activation of AHR by a high-affinity ligand during T(H)17 cell development markedly increases the proportion of T(H)17 T cells and their production of cytokines. CD4+ T cells from AHR-deficient mice can develop T(H)17 cell responses, but when confronted with AHR ligand fail to produce IL-22 and do not show enhanced T(H)17 cell development. AHR activation during induction of experimental autoimmune encephalomyelitis causes accelerated onset and increased pathology in wild-type mice, but not AHR-deficient mice. AHR ligands may therefore represent co-factors in the development of autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity / immunology*
  • Cell Differentiation
  • Cells, Cultured
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Environmental Exposure*
  • Environmental Pollutants / immunology*
  • Environmental Pollutants / toxicity
  • Hazardous Substances / immunology
  • Humans
  • Interleukin-17 / metabolism*
  • Interleukins / biosynthesis
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Aryl Hydrocarbon / deficiency
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Transduction, Genetic


  • Environmental Pollutants
  • Hazardous Substances
  • Interleukin-17
  • Interleukins
  • Ligands
  • Receptors, Aryl Hydrocarbon
  • interleukin-22