1. Division of Molecular Immunology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW71AA, UK
2. Institute for Medical Microbiology, University Hospital Essen, D-45122, Germany
3. Helmholtz Center for Infection Research, D-38124 Braunschweig, Germany
4. Ludwig Institute for Cancer Research, Brussels branch, and Experimental Medicine Unit, Universite Catholique de Louvain, B-1200 Brussels, Belgium

Correspondence to: Brigitta Stockinger¹ Correspondence and requests for materials should be addressed to B.S. (Email: bstocki@nimr.mrc.ac.uk).

Abstract

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor best known for mediating the toxicity of dioxin¹. Environmental factors are believed to contribute to the increased prevalence of autoimmune diseases, many of which are due to the activity of T_H17 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_H17 cell subset and its ligation results in the production of the T_H17 cytokine interleukin (IL)-22. AHR is also expressed in human T_H17 cells. Activation of AHR by a high-affinity ligand during T_H17 cell development markedly increases the proportion of T_H17 T cells and their production of cytokines. CD4⁺ T cells from AHR-deficient mice can develop T_H17 cell responses, but when confronted with AHR ligand fail to produce IL-22 and do not show enhanced T_H17 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.

1. Division of Molecular Immunology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW71AA, UK
2. Institute for Medical Microbiology, University Hospital Essen, D-45122, Germany
3. Helmholtz Center for Infection Research, D-38124 Braunschweig, Germany
4. Ludwig Institute for Cancer Research, Brussels branch, and Experimental Medicine Unit, Universite Catholique de Louvain, B-1200 Brussels, Belgium

Correspondence to: Brigitta Stockinger¹ Correspondence and requests for materials should be addressed to B.S. (Email: bstocki@nimr.mrc.ac.uk).

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.