Pyruvate dehydrogenase E2 complex

A transcription factor linking environmental toxins to autoimmunity

24 March 2008

NIMR scientists have discovered that a transcription factor that is well known for mediating the toxic effects of dioxin and other environmental toxins, is expressed in a population of immune cells that are involved in the pathology of many immune diseases. Activation of this transcription factor causes increased pathology in a murine autoimmune model, suggesting a mechanism by which environmental factors could play a role in the etiology of autoimmune diseases.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that is best known for mediating the toxicity of dioxin. A paper in Nature by Gitta Stockinger (pictured), from NIMR's Division of Molecular Immunology, demonstrates that AhR is expressed in a newly discovered T cell subset in mice and humans, termed TH17. These cells are crucially involved in the pathology of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.

photoproduct of tryptophan, generated by exposure to UV light, is an example of a potent AhR ligand. Exposure to this ligand during induction of experimental autoimmune encephalomyelitis (EAE) caused an acceleration in the development of disease and increased pathology.

Autoimmune diseases are multifactorial, depending on intrinsic factors such as genetics, hormones or age and environmental factors, including infections, diet, drugs and chemicals. The increasing prevalence of certain autoimmune diseases in highly industrialized countries is likely to be connected to such environmental factors. Our data linking a transcription factor responsive to environmental pollutants to the TH17 program opens intriguing possibilities regarding the potential of such factors to initiate or augment autoimmune conditions and warrant closer examination of a possible role of AhR in human autoimmune diseases.

Dr Stockinger

Original article

The research findings are published in full in:

Marc Veldhoen, Keiji Hirota, Astrid M. Westendorf, Jan Buer, Laure Dumoutier, Jean-Christophe Renauld and Brigitta Stockinger. (2008) 

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

Nature, epub ahead of print. Abstract

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