Abstract
In a time where “translational” science has become a mantra in the biomedical field, it is reassuring when years of research into a biological phenomenon suddenly points towards novel prevention or therapeutic approaches to disease, thereby demonstrating once again that basic science and translational science are intimately linked. The studies on the aryl hydrocarbon receptor (AHR) discussed here provide a perfect example of how years of basic toxicological research on a molecule, whose normal physiological function remained a mystery for so long, has now yielded a treasure trove of actionable information on the development of targeted therapeutics. Examples are autoimmunity, metabolic imbalance, inflammatory skin and gastro-intestinal diseases, cancer, development and perhaps ageing. Indeed, the AHR field no longer asks, “What does this receptor do in the absence of xenobiotics?” It now asks, “What doesn’t this receptor do?”.
Highlights
OverviewThe aryl hydrocarbon receptor (AHR), discovered 40 years ago, emerged initially as a novel class of protein: An orphan receptor that acts as a transcription factor, mediating the toxicity of chemicals from the environment
In 10 lecture sessions and a busy poster session, the meeting looked at aryl hydrocarbon receptor (AHR) signaling during development, its effect on basic functions, and at its involvement in metabolic disease, cancer, and immune-mediated diseases
Dr Perdew demonstrated for gut enterocytes that the turnover rate of this constantly selfrenewing epithelium depends on the activation of the AHR by diet-derived ligands
Summary
The aryl hydrocarbon receptor (AHR), discovered 40 years ago, emerged initially as a novel class of protein: An orphan receptor that acts as a transcription factor, mediating the toxicity of chemicals from the environment. The AHR has been called a link to the environment, a quorum sensor of bacteria, a pattern recognition receptor for chemicals, the mediator of the toxicity of polycyclic aromatic hydrocarbons (PAHs), and an attractive therapeutic target for cancer and immune diseases. These entire functions link AHRs ability to bind a variety of ligands, frequently present as mixtures, with complex temporal patterns of regulation. While the study of the complexity of AHR signaling and its effect on biological systems was initially the purview of toxicologists, the connection intrigues those studying developmental biology, immunology, various organ physiologies and resilience against stress, metabolism, cancer and those in search of valuable targets for prevention and therapy of a range of hard-to-treat diseases [1,2,3,4,5,6,7,8,9]
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