Role of AhR/ARNT system in skin homeostasis
Open accessAbstract
Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that binds to structurally diverse synthetic and naturally occurring chemicals including dioxins, flavonoids, tryptophan photoproducts, and Malassezia metabolites. Upon binding to its ligands, cytoplasmic AhR translocates to the nucleus, heterodimerizes with aryl hydrocarbon receptor nuclear translocator (ARNT), and mediates numerous biological and toxicological effects by inducing the transcription of various AhR-responsive genes. AhR ligation controls oxidation/antioxidation, epidermal barrier function, photo-induced response, melanogenesis, and innate immunity. This review summarizes recent advances in the understanding of the regulatory mechanisms of skin homeostasis mediated by the AhR/ARNT system.
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Air pollutants contain various exogenous ligands with high affinities for AhR, including PAHs and halogenated aromatic hydrocarbons such as TCDD, dimethylbenz[a]anthracene, methylcholanthrene, and benzo[a]pyrene.
“Air pollutants contain various exogenous ligands with high affinities for AhR, including PAHs and halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzodioxin (TCDD), dimethylbenz[a]anthracene, methylcholanthrene, and benzo[a]pyrene (BaP)30.”
From Air Pollution and Skin Diseases (2025) · cites this paper as [30]
The Introduction (page unavailable) identifies ubiquitous environmental contaminants, including dioxins and benzo[a]pyrene, as well-characterized high-affinity AhR ligands. The AhR/ARNT signaling section names TCDD and benzo[a]pyrene as ligands. Our copy does not identify dimethylbenz[a]anthracene or methylcholanthrene as AhR ligands, so the full list is not supported. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe ligand/AHR complex binds to specific DNA recognition sites and upregulates transcription of responsive genes, such as CYP1A1, leading to robust generation of reactive oxygen species.
“The ligand/AHR complex then binds to specific DNA recognition sites, namely, xenobiotic-responsive elements or dioxin-responsive elements, and upregulates the transcription of a series of responsive genes, such as CYP1A1 leading to a robust generation of reactive oxygen species [16,24].”
From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [16]
The AhR/ARNT signaling section says the ligand–AhR–ARNT complex binds xenobiotic- or dioxin-responsive elements and induces CYP1A1; its Fig. 1 caption says CYP1A1 metabolism of ligands such as dioxins produces many reactive oxygen species. But the oxidative-stress section says ROS production is ligand-dependent and that some AhR ligands activate the pathway without producing ROS. The claim overgeneralizes that outcome. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAHR is a xenobiotic chemical sensor expressed abundantly in epidermal keratinocytes.
“AHR is a xenobiotic chemical sensor that is expressed abundantly in epidermal keratinocytes [15,16].”
From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [16]
The Introduction describes AhR as a receptor for exogenous chemicals and says keratinocytes possess it; the AhR/ARNT signaling section links it to responses to xenobiotics. Neither passage establishes that AhR is expressed abundantly in epidermal keratinocytes. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAhR is widely expressed in the skin and is important in maintaining skin integrity and immune functions.
“The AhR is widely expressed in the skin, and is important in maintaining skin integrity and immune functions30.”
From Air Pollution and Skin Diseases (2025) · cites this paper as [30]
Various external and internal ligands, such as dioxins, polycyclic aromatic pollutants, benzo[a]pyrene, and phytochemicals, can bind to and activate AHR.
“Various external and internal ligands, such as dioxins, polycyclic aromatic pollutants, benzo[a]pyrene, and phytochemicals, can bind to and activate AHR [15,16].”
From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [16]
Various herbal and antioxidant phytochemicals activate AHR.
“Various herbal and antioxidant phytochemicals have been shown to activate AHR [16,17,19].”
From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [16]
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The clock gene brain and muscle Arnt-like protein-1 (BMAL1) is involved in hair growth
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Self-citationPolychlorinated dibenzofurans as a causal agent of fetal Yusho
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Self-citationOld King Coal - molecular mechanisms underlying an ancient treatment for atopic eczema.
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Environmental Air Pollutants Affecting Skin Functions with Systemic Implications
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Perillaldehyde inhibits AHR signaling and activates NRF2 antioxidant pathway in human keratinocytes
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Role of Aryl Hydrocarbon Receptor Activation in Inflammatory Chronic Skin Diseases
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Self-citationWhat are the 100 most cited fungal genera?
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Aryl hydrocarbon receptor (AhR) a possible target for the treatment of skin disease
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Yusho and its latest findings—A review in studies conducted by the Yusho Group
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Self-citationHost Immunity to Malassezia in Health and Disease
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Self-citationInteraction between AhR and HIF-1 signaling pathways mediated by ARNT/HIF-1β
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Quercetin protected the gut barrier in ulcerative colitis by activating aryl hydrocarbon receptor
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Aryl Hydrocarbon Receptor and Dioxin-Related Health Hazards—Lessons from Yusho
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Air Pollution and Skin Diseases
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“Air pollutants contain various exogenous ligands with high affinities for AhR, including PAHs and halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzodioxin (TCDD), dimethylbenz[a] anthracene, methylcholanthrene, and benzo[a]pyrene (BaP) 30 .”
Diosmin restores the skin barrier by targeting the aryl hydrocarbon receptor in atopic dermatitis
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Aryl Hydrocarbon Receptors: Evidence of Therapeutic Targets in Chronic Inflammatory Skin Diseases
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Malassezia spp. beyond The Mycobiota
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A Rose Extract Protects the Skin against Stress Mediators: A Potential Role of Olfactory Receptors
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Wutou decoction attenuates rheumatoid arthritis by modulating the Ahr/LOC101928120/SHC1 pathway
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Ligand-independent activation of AhR by hydroquinone mediates benzene-induced hematopoietic toxicity
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Galactomyces Ferment Filtrate Potentiates an Anti-Inflammaging System in Keratinocytes
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Self-citationExpression of CYP1A1, CYP1B1 and IL-1β in PBMCs and skin samples of PCB exposed individuals
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A novel oxidative stress marker of atopic dermatitis in infants: thiol–disulfide balance
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- Authors
- Furue, M., Takahara, M., Nakahara, T., & Uchi, H.
- Affiliations
- Kyushu University (JP)
- Corresponding author
- Furue, Masutaka
- Venue
- Archives of Dermatological Research
- Published
- 2014-06-26
- Volume
- 306
- Issue
- 9
- Pages
- 769-779
- ISSN
- 0003-9187 (ISSN-L)
- 0340-3696
- 1432-069X
- PMC
- PMC4220966
- OpenAlex
- W1991467319
- Cited by
- 175
- References
- 97
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 14 · 2023: 18 · 2022: 20 · 2021: 17 · 2020: 21 · 2019: 18 · 2018: 22 · 2017: 14 · 2016: 4 · 2015: 9 · 2014: 2
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Archives of Dermatological Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Ministry of Health, Labour and Welfare
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- aryl hydrocarbon receptor, ARNT, skin homeostasis, dioxins, flavonoids, tryptophan photoproducts, skin barrier function, melanogenesis, innate immunity, oxidative stress, transcriptional regulation, xenobiotic toxicity
- MeSH terms
- Animals, Gene Expression Regulation, Homeostasis, Humans, Immunity, Innate, Ligands, Melanins, Permeability, Skin, Skin Diseases, Signal Transduction, Receptors, Aryl Hydrocarbon, Oxidative Stress, Aryl Hydrocarbon Receptor Nuclear Translocator
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