Aryl Hydrocarbon Receptor in Keratinocytes Is Essential for Murine Skin Barrier Integrity
Open accessAbstract
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in adaptive cell functions, and it is highly active in the epidermis. AhR ligands can accelerate keratinocyte differentiation, but the precise role of AhR in the skin barrier is unknown. Our study showed that transepidermal water loss, a parameter of skin barrier integrity, is high in AhR-deficient mice. Experiments with conditionally AhR-deficient mouse lines identified keratinocytes as the primary cell population responsible for high transepidermal water loss. Electron microscopy showed weaker intercellular connectivity in the epidermis of keratinocytes in AhR-knockout mice, and gene expression analysis identified many barrier-associated genes as AhR targets. Moreover, AhR-deficient mice had higher interindividual differences in their microbiome. Interestingly, removing AhR ligands from the diet of wild-type mice mimicked AhR deficiency with respect to the impaired barrier; conversely, re-addition of the plant-derived ligand indole-3-carbinol rescued the barrier deficiency even in aged mice. Our results suggest that functional AhR expression is critical for skin barrier integrity and that AhR represents a molecular target for the development of therapeutic approaches for skin barrier diseases, including by dietary intervention.
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AHR has cell-specific roles in lymphocytes, intestinal epithelial cells, keratinocytes, Langerhans cells, and hematopoietic stem cells.
“Subsequent examination of this mouse crossed to various Cre models has unveiled a cell specific role for AHR in lymphocytes, intestinal epithelial cells, keratinocytes, Langerhans cells, and hematopoietic stem cells to name a few (Bennett et al., 2018; Haas et al., 2016; Hong et al., 2020; Li et al., 2018; Metidji et al., 2018)”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Haas et al., 2016
AHR itself is beneficial for the skin barrier, as AHR-deficient mice show skin inflammation, epidermal barrier dysfunction, and skin dysbiosis.
“In contrast to the toxic effects of persistently activated AHR, AHR itself is beneficial for the skin barrier, as the AHR-deficient mice show skin inflammation, epidermal barrier dysfunction, and skin dysbiosis (57, 58).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [57]
AHR is essential in maintaining normal skin barrier function and cutaneous homeostasis.
“AHR is essential in maintaining normal skin barrier function and cutaneous homeostasis (57, 58).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [57]
Barrier function is significantly disturbed in Ahr-null mice, indicating AHR plays a pivotal role in skin barrier integrity.
“In addition, barrier function is significantly disturbed in Ahr-null mice, indicating that AHR plays a pivotal role in skin barrier integrity [30].”
From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [30]
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- Authors
- Haas, K., Weighardt, H., Deenen, R., Köhrer, K., Clausen, B., Zahner, S., Boukamp, P., Bloch, W., Krutmann, J., & Esser, C.
- Affiliations
- Leibniz Institute of Environmental Medicine (DE)
- University of Bonn (DE)
- Heinrich Heine University Düsseldorf (DE)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- La Jolla Institute for Immunology (US)
- German Sport University Cologne (DE)
- Corresponding author
- Esser, Charlotte
- ORCID
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 136
- Issue
- 11
- Pages
- 2260-2269
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2504117369
- Cited by
- 125
- References
- 73
- Citations by year
- 2026: 15 · 2025: 10 · 2024: 6 · 2023: 17 · 2022: 11 · 2021: 11 · 2020: 12 · 2019: 13 · 2018: 17 · 2017: 11 · 2016: 2
- FWCI
- 17.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- aryl hydrocarbon receptor, keratinocytes, skin barrier integrity, transepidermal water loss, epidermis, skin microbiome, indole-3-carbinol, dietary intervention, AhR ligands, keratinocyte differentiation
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Disease Models, Animal, DNA, Gene Expression Regulation, Mice, Inbred C57BL, Microscopy, Electron, Skin Diseases, Keratinocytes, Receptors, Aryl Hydrocarbon, Mice, Basic Helix-Loop-Helix Proteins
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