Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 21, Issue 24, Pages -Publisher
MDPI
DOI: 10.3390/ijms21249614
Keywords
AHR; Ah receptor; agonist; tryptophan; cytokines; microbiome; indole
Funding
- National Institutes of Health [ES028244]
- USDA National Institute of Food and Federal Appropriations [PEN04607, 1009993]
- NIFA [913554, 1009993] Funding Source: Federal RePORTER
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Increasingly, the aryl hydrocarbon receptor (AHR) is being recognized as a sensor for endogenous and pseudo-endogenous metabolites, and in particular microbiota and host generated tryptophan metabolites. One proposed explanation for this is the role of the AHR in innate immune signaling within barrier tissues in response to the presence of microorganisms. A number of cytokine/chemokine genes exhibit a combinatorial increase in transcription upon toll-like receptors and AHR activation, supporting this concept. The AHR also plays a role in the enhanced differentiation of intestinal and dermal epithelium leading to improved barrier function. Importantly, from an evolutionary perspective many of these tryptophan metabolites exhibit greater activation potential for the human AHR when compared to the rodent AHR. These observations underscore the importance of the AHR in barrier tissues and may lead to pharmacologic therapeutic intervention.
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