MRC National Institute for Medical Research, London
Science for Health
Eat your broccoli
13 October 2011
Scientists at NIMR have found that nutrients found in vegetables such as broccoli help to maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. The research is published in Cell.
Epithelial barriers, surfaces such as the skin and the intestine, are colonised with a controlled composition and number of microorganisms. In the intestine many of these aid in nutrient processing and provide essential metabolic compounds. Disturbances to this delicate equilibrium can give rise to disease such as inflammatory bowel disease. Although many microorganisms are beneficial, the tissues need protection against assault from pathogenic microorganisms. A first line of defence is the physical obstruction provided by a single or multi-cell layer, the epithelial barrier. Underneath the epithelial barrier there is a network of immune cells, predominantly consisting of specialised intraepithelial lymphocytes (IELs). These are important as a first line of defence as well as in epithelial barrier organisation and wound repair. They populate these sites before birth in preparation for subsequent colonisation with microorganisms.
Marc Veldhoen (pictured), working in Gitta Stockinger’s lab in NIMR’s Division of Molecular Immunology, has shown that the aryl hydrocarbon receptor (AhR) is crucially important for the maintenance of intestinal epithelial cells (IEL). AhR maintains IEL numbers in both the skin and the intestine and therefore helps to maintain barrier integrity. AhR is a ligand-dependent transcription factor best known for mediating the toxicity of dioxin and therefore also known as dioxin receptor.
The lack of AhR in AhR-deficient mice or of AhR ligands in special diets resulted in increased microbial load and vulnerability to epithelial damage in mouse models of colitis. AhR activity was found to be regulated by dietary components found in cruciferous vegetables, such as broccoli. This provides a mechanistic link between dietary components, the intestinal immune system and the microbiota. Furthermore, the data reveal an important physiological function of the AhR - beyond that of mediating the toxicity of xenobiotics - in the homeostasis of epithelial barriers.
Intestinal and skin gd T cells depend on AhR for survival
Click image to view at full-size
Tissue samples from control (upper panels) or AhR-deficient (lower panels) mice were stained with antibodies against EpCam (green) and TCRγδ (red) in the small intestine (F) or TCRVγ3 (green) in the skin (mice aged 8 weeks).
These data highlight the evolutionarily highly conserved AhR system as a previously unknown link between external environmental stimuli and the maintenance of specialised immune cells that influence barrier integrity. They provide a molecular basis for the importance of cruciferous vegetable-derived phytonutrients as part of a healthy diet to sustain important elements of the immune system and control bacterial colonisation
Gitta Stockinger
Marc Veldhoen moved to the Babraham Institute in 2010, but most of the work described here was carried out at NIMR. This year he has been awarded an ERC Starting Independent Researcher Grant from the European Research Council to continue this research at Babraham.
Original article
Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation
Ying Li, Silvia Innocentin, David R. Withers, Natalie A. Roberts, Alec R. Gallagher, Elena F. Grigorieva, Christoph Wilhelm and Marc Veldhoen (2011).
Cell, Epub ahead of print. Publisher abstract.
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