Specialized intraepithelial T lymphocytes (IELs) reside at locations where epithelia provide a barrier between the host and the environment, such as the skin and intestine. These IELs help defend the host against microorganisms and participate in wound repair. Li et al. found that, under basal conditions, ex vivo mouse IELs showed increased abundance of the mRNA encoding the aryl hydrocarbon receptor (AhR) transcription factor compared with T cells derived from lymph nodes, whereas skin and intestinal IELs were lost in AhR-deficient mice. The loss of skin and intestinal IELs in AhR-deficient mice could not be attributed to defects in production or homing; rather, it appeared to result from compromised IEL maintenance at epithelia. Experiments with chimeric mice, or mice with lymphocyte-specific deletion of the AhR, indicated that IEL maintenance depended on T-cell intrinsic AhR function. The abundance of the mRNAs encoding the AhR and its target gene Cyp1a1 was decreased in the intestines of mice fed a synthetic purified diet lacking AhR ligands compared with those fed a standard diet, as was IEL abundance—deficiencies reversed by dietary supplementation with a phytochemical found in cruciferous vegetables that is a precursor to AhR ligands. Consistent with IEL loss, the synthetic diet led to decreased intestinal abundance of mRNAs encoding several factors associated with antimicrobial activity and wound healing and an increased bacterial load in the small intestine. AhR-deficient mice and control mice fed the synthetic diet showed enhanced immune activation in the colon and accelerated weight loss in a model of chemically induced colitis exacerbated by bacterial dissemination; histological analysis revealed exaggerated epithelial immunopathology with colitis in the AhR-deficient mice. Thus, the authors conclude that activation of AhRs in intestinal IELs, which can be mediated by ligands derived from cruciferous vegetables, plays a key role in the intestinal immune system.
Y. Li, S. Innocentin, D. R. Withers, N. A. Roberts, A. R. Gallagher, E. F. Grigorieva, C. Wilhelm, M. Veldhoen, Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 147, 629–640 (2011). [PubMed]