The Aryl Hydrocarbon Receptor in Barrier Organ Physiology, Immunology, and Toxicology
Abstract
The aryl hydrocarbon receptor (AhR) is an evolutionarily old transcription factor belonging to the Per-ARNT-Sim-basic helix-loop-helix protein family. AhR translocates into the nucleus upon binding of various small molecules into the pocket of its single-ligand binding domain. AhR binding to both xenobiotic and endogenous ligands results in highly cell-specific transcriptome changes and in changes in cellular functions. We discuss here the role of AhR for immune cells of the barrier organs: skin, gut, and lung. Both adaptive and innate immune cells require AhR signaling at critical checkpoints. We also discuss the current two prevailing views-namely, 1) AhR as a promiscuous sensor for small chemicals and 2) a role for AhR as a balancing factor for cell differentiation and function, which is controlled by levels of endogenous high-affinity ligands. AhR signaling is considered a promising drug and preventive target, particularly for cancer, inflammatory, and autoimmune diseases. Therefore, understanding its biology is of great importance.
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This idea has been supported and expanded upon recently as additional evidence emerges detailing missing or impaired populations of resident immune cells in adult null mice at barrier tissues like the lung, intestine, and skin.
“This idea has been supported and expanded upon recently as additional evidence emerges detailing missing or impaired populations of resident immune cells in adult null mice at barrier tissues like the lung, intestine, and skin (Esser & Rannug, 2015; Kiss et al., 2011; Lee et al., 2012; Li et al., 2018; Qiu et al., 2012; Stockinger et al., 2014).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Esser & Rannug, 2015
The AHR is now commonly thought of as being highly active in the mounting and coordination of immune responses in barrier organs like the skin, gut, and lung in addition to the previously defined roles of xenobiotic metabolism and toxicity.
“The AHR is now commonly thought of as being highly active in the mounting and coordination of immune responses in barrier organs like the skin, gut, and lung in addition to the previously defined roles of xenobiotic metabolism and toxicity (Díaz-Díaz et al., 2018; Esser & Rannug, 2015).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Esser & Rannug, 2015
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“…Avenue, Madison, WI 53706, USA 2021 Informa UK Limited, trading as Taylor & Francis Group local physiological chemistries, particularly at barrier tissues and during times of stress, and to orchestrate appropriate biological responses (Esser and Rannug 2015; Haas et al. 2016; Avilla et al. 2020).”
BackgroundInfluential
- Authors
- Esser, C., & Rannug, A.
- Affiliations
- Karolinska Institutet (SE)
- Venue
- Pharmacological Reviews
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 67
- Issue
- 2
- Pages
- 259-279
- ISSN
- 0031-6997 (ISSN-L)
- OpenAlex
- W2124210208
- Cited by
- 501
- References
- 15
- Citations by year
- 2026: 24 · 2025: 33 · 2024: 41 · 2023: 52 · 2022: 44 · 2021: 64 · 2020: 62 · 2019: 46 · 2018: 52 · 2017: 40 · 2016: 27 · 2015: 15
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- aryl hydrocarbon receptor, skin, intestine, lung, immune cells, endogenous ligands, transcription factor signaling, cell differentiation, innate immunity, adaptive immunity, therapeutic target, cancer, inflammatory diseases, autoimmune disease
- MeSH terms
- Animals, Cell Differentiation, Humans, Immunity, Cellular, Immunity, Innate, Ligands, Lung, Models, Biological, Skin, Skin Physiological Phenomena, Xenobiotics, Signal Transduction, Receptors, Aryl Hydrocarbon, Gastrointestinal Tract, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins
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