It was very exciting to have the opportunity to report on this lecture by Brigitta Stockinger from the National Institute for Medical Research, London. The Keynote Medical Research Council Lecture was entitled "Environmental Influences on the Immune System via the Ahr." New members of the SOT may not be completely familiar with the buzz and interest the AhR created 20 years ago when the AhR was cloned and the gene eventually knocked out in mice. For several years that followed it was hard to walk through a poster session without learning more and more about the activity of this interesting molecular system. For really the first time in history, it was demonstrated that toxicity of an environmental chemical may be disrupting very specific systems, not unlike a pharmaceutical. The cloning and knockout of the Ahr ushered in this new paradigm in mechanistic-based toxicology.
What remained an open question about the Ahr back then was always a question of what is it doing when we are not throwing dioxin at it. The system is highly conserved and ubiquitous suggesting a major role in biology. The work of Dr. Stockinger, among others, has brought this question into reality and provided significant detail behind it. It started with the observation that despite the very ubiquitous nature of Ahr expression, in subsets of T cells, the expression is very selective. This led to the discovery that Ahr knockout mice are deficient in the TH17 subset of T cells. Dr. Stockinger proceeded to walk the audience through the story then of the discovery of a high-affinity endogenous ligand and the role of the Ahr in the burst of metabolic activity that regulates this ligand.
What has become obvious based on this really elegant work is that the Ahr really is designed to respond to environments; something that confirms the suspicions of the old guard of AhR researchers. Stockinger’s lab has proven how AhR plays a key role in barrier functions; our barriers being skin, and the mucosal linings of lung and intestine. In the intestine, AhR creates a feedback symbiosis with bacteria to control certain populations of bacteria in the gut as well as tempers inflammation by responding to molecules from cruciferous vegetables. The take away message is two fold. On a professional level, toxicologists should be considering the pathway of interest not just in mediating toxicity, but in mediating adaptive responses to our environments. The second takeaway, which I hope to implore to my kids, is to eat your vegetables!
This blog discusses the SOT Annual Meeting and ToxExpo Featured Session, Keynote Medical Research Council (MRC) Lecture: Environmental Influences on the Immune System via the Aryl Hydrocarbon Receptor