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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 July 2020) | Viewed by 54101

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Prof. Dr. Charlotte Esser

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IUF – Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, D-40225 Düsseldorf, Germany
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DEar Colleagues,

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that translocates to the nucleus and initiates the transcription of many target genes upon binding of the relevant ligands. AHR is of increasing interest in many areas of biology and medicine. Its rather chemical name results from its first characterized function in xenobiotic metabolism and the AHR-dependent toxicity of various aryls, especially dioxins and dioxin-like compounds. In recent years, many endogenous and dietary ligands have been identified, though still a far cry from the multitude of environmental pollutants. Moreover, in humans, evolution seems to have shaped differential AHR responses that correspond to certain ligand classes.

AHR targets many physiological processes both directly and indirectly. It was found to be involved in the differentiation and function of adaptive and innate immune cells. AHR is important for wound healing, cancer evasion, kidney functions, macular degeneration, the commensal microbiome, aging, sensing of light/UV irradiation in the skin, possibly depression, and many more. This breadth is both exciting and vexing; we can expect more to come. At the same time, more research is needed in the light of these new findings, looking at the toxicity of AHR ligands in heavily polluted areas or in newly developing pollution situations, like e-waste reclamation.

Finally, the vast area of how to therapeutically harness AHR ligands has attracted many new research groups and industrial stakeholders into the field. On the biochemical side, advances are made to dissect the structure–activity relationship of ligand-bound AHR at the promoter. This information is critical for advancing the development of therapeutic ligands and to improve screening approaches that are more directed than the current ‘trial-and-error’ approaches.

In this Special Issue of IJMS, we wish to offer a platform for high-quality publications on these various aspects of AHR research. Bringing together the different aspects into one issue will hopefully trigger synergy and also be of interest for non-AHR researchers.

Prof. Dr. Charlotte Esser
Guest Editor

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Keywords

AHR in immunology
AHR in cancer research
biochemistry of AHR and AHR-signaling
AHR involvement in diseases
AHR and metabolism
epidemiology of AHR ligand exposure
AHR ligands in therapy and prevention
adverse outcome pathways and AHR

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Aryl Hydrocarbon Receptor in Biology and Toxicology in International Journal of Molecular Sciences (14 articles)

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20 pages, 1823 KiB

Open AccessArticle

Meta-Analysis of Transcriptome Data Detected New Potential Players in Response to Dioxin Exposure in Humans

by Evgeniya Oshchepkova, Yana Sizentsova, Daniil Wiebe, Victoria Mironova and Nikolay Kolchanov

Int. J. Mol. Sci. 2020, 21(21), 7858; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217858 - 23 Oct 2020

Cited by 4 | Viewed by 2004

Abstract

Dioxins are one of the most potent anthropogenic poisons, causing systemic disorders in embryonic development and pathologies in adults. The mechanism of dioxin action requires an aryl hydrocarbon receptor (AhR), but the downstream mechanisms are not yet precisely clear. Here, we performed a meta-analysis of all available transcriptome datasets taken from human cell cultures exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Differentially expressed genes from different experiments overlapped partially, but there were a number of those genes that were systematically affected by TCDD. Some of them have been linked to toxic dioxin effects, but we also identified other attractive targets. Among the genes that were affected by TCDD, there are functionally related gene groups that suggest an interplay between retinoic acid, AhR, and Wnt signaling pathways. Next, we analyzed the upstream regions of differentially expressed genes and identified potential transcription factor (TF) binding sites overrepresented in the genes responding to TCDD. Intriguingly, the dioxin-responsive element (DRE), the binding site of AhR, was not overrepresented as much as other cis-elements were. Bioinformatics analysis of the AhR binding profile unveils potential cooperation of AhR with E2F2, CTCFL, and ZBT14 TFs in the dioxin response. We discuss the potential implication of these predictions for further dioxin studies. Full article

(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology 2.0)

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15 pages, 2455 KiB

Open AccessArticle

TRPV1 Hyperfunction Involved in Uremic Toxin Indoxyl Sulfate-Mediated Renal Tubular Damage

by Chien-Lin Lu, Chun-Hou Liao, Kuo-Cheng Lu and Ming-Chieh Ma

Int. J. Mol. Sci. 2020, 21(17), 6212; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176212 - 27 Aug 2020

Cited by 14 | Viewed by 2200

Abstract

Indoxyl sulfate (IS) is accumulated during severe renal insufficiency and known for its nephrotoxic properties. Transient receptor potential vanilloid 1 (TRPV1) is present in the kidney and acts as a renal sensor. However, the mechanism underlying IS-mediated renal tubular damage in view of TRPV1 is lacking. Here, we demonstrated that TRPV1 was expressed in tubular cells of Lilly Laboratories cell-porcine kidney 1 (LLC-PK₁) and Madin-Darby canine kidney cells (MDCK). IS treatment in both cells exhibited tubular damage with increased LDH release and reduced cell viability in dose- and time-dependent manners. MDCK, however, was more vulnerable to IS. We, therefore, investigated MDCK cells to explore a more detailed mechanism. Interestingly, IS-induced tubular damage was markedly attenuated in the presence of selective TRPV1 blockers. IS showed no effect on TRPV1 expression but significantly increased arachidonate 12-lipoxygenase (ALOX12) protein, mRNA expression, and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) amounts in a dose-dependent manner, indicating that the ALOX12/12(S)-HETE pathway induced TRPV1 hyperfunction in IS-mediated tubulotoxicity. Blockade of ALOX12 by cinnamyl-3,4-dihydroxy-α-cyanocinnamate or baicalein attenuated the effects of IS. Since aryl hydrocarbon receptor (AhR) activation after IS binding is crucial in mediating cell death, here, we found that the AhR blockade not only ameliorated tubular damage but also attenuated ALOX12 expression and 12(S)-HETE production caused by IS. The uremic toxic adsorbent AST-120, however, showed little effect on ALOX12 and 12(S)-HETE, as well as IS-induced cell damage. These results clearly indicated that IS activated AhR and then upregulated ALOX12, and this induced endovanilloid 12(S)-HETE synthesis and contributed to TRPV1 hyperfunction in IS-treated tubular cells. Further study on TRPV1 may attenuate kidney susceptibility to the functional loss of end-stage kidney disease via IS. Full article

(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology 2.0)

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21 pages, 7735 KiB

Open AccessArticle

Role of Flavonoids in the Prevention of AhR-Dependent Resistance During Treatment with BRAF Inhibitors

by Héloïse M. Leclair, Nina Tardif, Anaïs Paris, Marie-Dominique Galibert and Sébastien Corre

Int. J. Mol. Sci. 2020, 21(14), 5025; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145025 - 16 Jul 2020

Cited by 8 | Viewed by 2427

Abstract

BRAF and MEK inhibitors (BRAFi and MEKi) are the standard of care for the treatment of metastatic melanoma in patients with BRAF^V600E mutations, greatly improving progression-free survival. However, the acquisition of resistance to BRAFi and MEKi remains a difficult clinical challenge, with limited therapeutic options available for these patients. Here, we investigated the therapeutic potential of natural flavonoids as specific AhR (Aryl hydrocarbon Receptor) transcription factor antagonists in combination with BRAFi. Experimental Design: Experiments were performed in vitro and in vivo with various human melanoma cell lines (mutated for BRAF^V600E) sensitive or resistant to BRAFi. We evaluated the role of various flavonoids on cell sensitivity to BRAFi and their ability to counteract resistance and the invasive phenotype of melanoma. Results: Flavonoids were highly effective in potentiating BRAFi therapy in human melanoma cell lines by increasing sensitivity and delaying the pool of resistant cells that arise during treatment. As AhR antagonists, flavonoids counteracted a gene expression program associated with the acquisition of resistance and phenotype switching that leads to an invasive and EMT-like phenotype. Conclusions: The use of natural flavonoids opens new therapeutic opportunities for the treatment of patients with BRAF-resistant disease. Full article

(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology 2.0)

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22 pages, 4721 KiB

Open AccessArticle

Selective Autophagy Maintains the Aryl Hydrocarbon Receptor Levels in HeLa Cells: A Mechanism That Is Dependent on the p23 Co-Chaperone

by Yujie Yang and William K. Chan

Int. J. Mol. Sci. 2020, 21(10), 3449; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103449 - 13 May 2020

Cited by 9 | Viewed by 3102

Abstract

The aryl hydrocarbon receptor (AHR) is an environmental sensing molecule which impacts diverse cellular functions such as immune responses, cell growth, respiratory function, and hematopoietic stem cell differentiation. It is widely accepted that the degradation of AHR by 26S proteasome occurs after ligand activation. Recently, we discovered that HeLa cells can modulate the AHR levels via protein degradation without exogenous treatment of a ligand, and this degradation is particularly apparent when the p23 content is down-regulated. Inhibition of autophagy by a chemical agent (such as chloroquine, bafilomycin A1, or 3-methyladenine) increases the AHR protein levels in HeLa cells whereas activation of autophagy by short-term nutrition deprivation reduces its levels. Treatment of chloroquine retards the degradation of AHR and triggers physical interaction between AHR and LC3B. Knockdown of LC3B suppresses the chloroquine-mediated increase of AHR. Down-regulation of p23 promotes AHR degradation via autophagy with no change of the autophagy-related gene expression. Although most data in this study were derived from HeLa cells, human lung (A549), liver (Hep3B), and breast (T-47D and MDA-MB-468) cells also exhibit AHR levels sensitive to chloroquine treatment and AHR–p62/LC3 interactions. Here we provide evidence supporting that AHR undergoes the p62/LC3-mediated selective autophagy in HeLa cells. Full article

(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology 2.0)

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15 pages, 2470 KiB

Open AccessArticle

Antimigraine Drug Avitriptan Is a Ligand and Agonist of Human Aryl Hydrocarbon Receptor that Induces CYP1A1 in Hepatic and Intestinal Cells

by Barbora Vyhlídalová, Kristýna Krasulová, Petra Pečinková, Karolína Poulíková, Radim Vrzal, Zdeněk Andrysík, Aneesh Chandran, Sridhar Mani and Zdenek Dvorak

Int. J. Mol. Sci. 2020, 21(8), 2799; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082799 - 17 Apr 2020

Cited by 5 | Viewed by 3378

Abstract

The efforts for therapeutic targeting of the aryl hydrocarbon receptor (AhR) have emerged in recent years. We investigated the effects of available antimigraine triptan drugs, having an indole core in their structure, on AhR signaling in human hepatic and intestinal cells. Activation of AhR in reporter gene assays was observed for Avitriptan and to a lesser extent for Donitriptan, while other triptans were very weak or no activators of AhR. Using competitive binding assay and by homology docking, we identified Avitriptan as a low-affinity ligand of AhR. Avitriptan triggered nuclear translocation of AhR and increased binding of AhR in CYP1A1 promotor DNA, as revealed by immune-fluorescence microscopy and chromatin immune-precipitation assay, respectively. Strong induction of CYP1A1 mRNA was achieved by Avitriptan in wild type but not in AhR-knockout, immortalized human hepatocytes, implying that induction of CYP1A1 is AhR-dependent. Increased levels of CYP1A1 mRNA by Avitriptan were observed in human colon carcinoma cells LS180 but not in primary cultures of human hepatocytes. Collectively, we show that Avitriptan is a weak ligand and activator of human AhR, which induces the expression of CYP1A1 in a cell-type specific manner. Our data warrant the potential off-label therapeutic application of Avitriptan as an AhR-agonist drug. Full article

(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology 2.0)

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17 pages, 3909 KiB

Open AccessArticle

Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization

by Barbora Vyhlídalová, Kristýna Krasulová, Petra Pečinková, Adéla Marcalíková, Radim Vrzal, Lenka Zemánková, Jan Vančo, Zdeněk Trávníček, Jan Vondráček, Martina Karasová, Sridhar Mani and Zdeněk Dvořák

Int. J. Mol. Sci. 2020, 21(7), 2614; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072614 - 09 Apr 2020

Cited by 73 | Viewed by 5324

Abstract

We examined the effects of gut microbial catabolites of tryptophan on the aryl hydrocarbon receptor (AhR). Using a reporter gene assay, we show that all studied catabolites are low-potency agonists of human AhR. The efficacy of catabolites differed substantially, comprising agonists with no or low (i3-propionate, i3-acetate, i3-lactate, i3-aldehyde), medium (i3-ethanol, i3-acrylate, skatole, tryptamine), and high (indole, i3-acetamide, i3-pyruvate) efficacies. We displayed ligand-selective antagonist activities by i3-pyruvate, i3-aldehyde, indole, skatole, and tryptamine. Ligand binding assay identified low affinity (skatole, i3-pyruvate, and i3-acetamide) and very low affinity (i3-acrylate, i3-ethanol, indole) ligands of the murine AhR. Indole, skatole, tryptamine, i3-pyruvate, i3-acrylate, and i3-acetamide induced CYP1A1 mRNA in intestinal LS180 and HT-29 cells, but not in the AhR-knockout HT-29 variant. We observed a similar CYP1A1 induction pattern in primary human hepatocytes. The most AhR-active catabolites (indole, skatole, tryptamine, i3-pyruvate, i3-acrylate, i3-acetamide) elicited nuclear translocation of the AhR, followed by a formation of AhR-ARNT heterodimer and enhanced binding of the AhR to the CYP1A1 gene promoter. Collectively, we comprehensively characterized the interactions of gut microbial tryptophan catabolites with the AhR, which may expand the current understanding of their potential roles in intestinal health and disease. Full article

(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology 2.0)

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21 pages, 2430 KiB

Open AccessArticle

AHR Signaling Dampens Inflammatory Signature in Neonatal Skin γδ T Cells

by Katja Merches, Alfonso Schiavi, Heike Weighardt, Swantje Steinwachs, Nadine Teichweyde, Irmgard Förster, Katrin Hochrath, Beatrix Schumak, Natascia Ventura, Patrick Petzsch, Karl Köhrer and Charlotte Esser

Int. J. Mol. Sci. 2020, 21(6), 2249; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062249 - 24 Mar 2020

Cited by 11 | Viewed by 4443

Abstract

Background Aryl hydrocarbon receptor (AHR)-deficient mice do not support the expansion of dendritic epidermal T cells (DETC), a resident immune cell population in the murine epidermis, which immigrates from the fetal thymus to the skin around birth. Material and Methods In order to identify the gene expression changes underlying the DETC disappearance in AHR-deficient mice, we analyzed microarray RNA-profiles of DETC, sorted from the skin of two-week-old AHR-deficient mice and their heterozygous littermates. In vitro studies were done for verification, and IL-10, AHR repressor (AHRR), and c-Kit deficient mice analyzed for DETC frequency. Results We identified 434 annotated differentially expressed genes. Gene set enrichment analysis demonstrated that the expression of genes related to proliferation, ion homeostasis and morphology differed between the two mouse genotypes. Importantly, with 1767 pathways the cluster-group “inflammation” contained the majority of AHR-dependently regulated pathways. The most abundant cluster of differentially expressed genes was “inflammation.” DETC of AHR-deficient mice were inflammatory active and had altered calcium and F-actin levels. Extending the study to the AHRR, an enigmatic modulator of AHR-activity, we found approximately 50% less DETC in AHRR-deficient mice than in wild-type-littermates. Conclusion AHR-signaling in DETC dampens their inflammatory default potential and supports their homeostasis in the skin. Full article

(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology 2.0)

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17 pages, 6592 KiB

Open AccessArticle

Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation

by Hye Ran Kim, Seok Young Kang, Hye One Kim, Chun Wook Park and Bo Young Chung

Int. J. Mol. Sci. 2020, 21(6), 2195; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062195 - 22 Mar 2020

Cited by 33 | Viewed by 5337

Abstract

Aryl hydrocarbon receptor (AhR) and autophagy reportedly regulate immune responses in the skin. This study explored the effects of AhR activation on autophagy in human keratinocytes, and the relevance of AhR and autophagy in psoriasis pathogenesis. AhR activation by 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) repressed autophagy, while autophagy inhibition induced AhR activation in HaCaT cells and normal human epidermal keratinocytes (NHEKs). A particularly strong interaction between AhR and autophagy was observed in proinflammatory cytokines-stimulated keratinocytes, an in vitro model of psoriasis. In skin biopsies from psoriasis patients, a similar impact of AhR on autophagy and inflammation was observed. AhR inhibition blocked TCDD- and chloroquine-induced p65NF-κB and p38MAPK phosphorylation in proinflammatory cytokines-stimulated HaCaT cells. Moreover, higher expression of AhR and CYP1A1, and lower expression of LC3, were detected in psoriatic skin tissues, compared to the controls. These data demonstrated that AhR modulated autophagy leads to skin inflammation in human keratinocytes via the p65NF-κB/p38MAPK signaling pathways, suggesting that AhR signaling and autophagy might be involved in the pathogenesis of chronic inflammatory disorders such as psoriasis. Full article

(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology 2.0)

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12 pages, 3681 KiB

Open AccessArticle

Aryl Hydrocarbon Receptor in Post-Mortem Hippocampus and in Serum from Young, Elder, and Alzheimer’s Patients

by Nicte Alaide Ramos-García, Marisol Orozco-Ibarra, Enrique Estudillo, Guillermo Elizondo, Erick Gómez Apo, Laura Graciela Chávez Macías, Ana Luisa Sosa-Ortiz and Mónica Adriana Torres-Ramos

Int. J. Mol. Sci. 2020, 21(6), 1983; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21061983 - 14 Mar 2020

Cited by 39 | Viewed by 3667

Abstract

One of the characteristics of the cerebral aging process is the presence of chronic inflammation through glial cells, which is particularly significant in neurodegeneration. On the other hand, it has been demonstrated that the aryl hydrocarbon receptor (AHR) participates in the inflammatory response. Currently, evidence in animal models shows that the hallmarks of aging are associated with changes in the AHR levels. However, there is no information concerning the behavior and participation of AHR in the human aging brain or in Alzheimer’s disease (AD). We evaluated the expression of AHR in human hippocampal post-mortem tissue and its association with reactive astrocytes by immunohistochemistry. Besides this, we analyzed through ELISA the AHR levels in blood serum from young and elder participants, and from AD patients. The levels of AHR and glial fibrillar acid protein were higher in elder than in young post-mortem brain samples. AHR was localized mainly in the cytosol of astrocytes and displayed a pattern that resembles extracellular vesicles; this latter feature was more conspicuous in AD subjects. We found higher serum levels of AHR in AD patients than in the other participants. These results suggest that AHR participates in the aging process, and probably in the development of neurodegenerative diseases like AD. Full article

(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology 2.0)

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Review

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The Landscape of AhR Regulators and Coregulators to Fine-Tune AhR Functions

by Marco Gargaro, Giulia Scalisi, Giorgia Manni, Giada Mondanelli, Ursula Grohmann and Francesca Fallarino

Int. J. Mol. Sci. 2021, 22(2), 757; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020757 - 13 Jan 2021

Cited by 29 | Viewed by 6305

Abstract

The aryl-hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates numerous cellular responses. Originally investigated in toxicology because of its ability to bind environmental contaminants, AhR has attracted enormous attention in the field of immunology in the last 20 years. In addition, the discovery of endogenous and plant-derived ligands points to AhR also having a crucial role in normal cell physiology. Thus, AhR is emerging as a promiscuous receptor that can mediate either toxic or physiologic effects upon sensing multiple exogenous and endogenous molecules. Within this scenario, several factors appear to contribute to the outcome of gene transcriptional regulation by AhR, including the nature of the ligand as such and its further metabolism by AhR-induced enzymes, the local tissue microenvironment, and the presence of coregulators or specific transcription factors in the cell. Here, we review the current knowledge on the array of transcription factors and coregulators that, by interacting with AhR, tune its transcriptional activity in response to endogenous and exogenous ligands. Full article

(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology 2.0)

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13 pages, 2034 KiB

Open AccessReview

Anti-Aging Physiological Roles of Aryl Hydrocarbon Receptor and Its Dietary Regulators

by Eva Serna, Cristina Cespedes and Jose Vina

Int. J. Mol. Sci. 2021, 22(1), 374; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010374 - 31 Dec 2020

Cited by 7 | Viewed by 3613

Abstract

The vast majority of the literature on the aryl hydrocarbon receptor is concerned with its functions in xenobiotic detoxification. However, in the course of evolution, this receptor had to have physiological (rather than toxicological) functions. Our aim was to review the aryl hydrocarbon receptor’s role in the physiological functions involved in aging. This study was performed by searching the MEDLINE and Google Academic databases. A total of 34 articles were selected that focused specifically on the aryl hydrocarbon receptor and aging, the aryl hydrocarbon receptor and physiological functions, and the combination of both. This receptor’s main physiological functions (mediated by the modulation of gene expression) were cell regeneration, the immune reaction, intestinal homeostasis, and cell proliferation. Furthermore, it was shown that the loss of this receptor led to premature aging. This process may be caused by the dysregulation of hematopoietic stem cells, loss of glucose and lipid homeostasis, increase in inflammation, and deterioration of the brain. We conclude that the aryl hydrocarbon receptor, apart from its well-established role in xenobiotic detoxication, plays an important role in physiological functions and in the aging process. Modulation of the signaling pathway of this receptor could be a therapeutic target of interest in aging. Full article

(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology 2.0)

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17 pages, 2216 KiB

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The Aryl Hydrocarbon Receptor: A Mediator and Potential Therapeutic Target for Ocular and Non-Ocular Neurodegenerative Diseases

by Mayur Choudhary and Goldis Malek

Int. J. Mol. Sci. 2020, 21(18), 6777; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186777 - 16 Sep 2020

Cited by 17 | Viewed by 7564

Abstract

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which senses environmental, dietary or metabolic signals to mount a transcriptional response, vital in health and disease. As environmental stimuli and metabolic products have been shown to impact the central nervous system (CNS), a burgeoning area of research has been on the role of the AHR in ocular and non-ocular neurodegenerative diseases. Herein, we summarize our current knowledge, of AHR-controlled cellular processes and their impact on regulating pathobiology of select ocular and neurodegenerative diseases. We catalogue animal models generated to study the role of the AHR in tissue homeostasis and disease pathogenesis. Finally, we discuss the potential of targeting the AHR pathway as a therapeutic strategy, in the context of the maladies of the eye and brain. Full article

(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology 2.0)

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28 pages, 1066 KiB

Open AccessReview

Epigenetic Regulations of AhR in the Aspect of Immunomodulation

by Anna Wajda, Joanna Łapczuk-Romańska and Agnieszka Paradowska-Gorycka

Int. J. Mol. Sci. 2020, 21(17), 6404; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176404 - 03 Sep 2020

Cited by 10 | Viewed by 3668

Abstract

Environmental factors contribute to autoimmune disease manifestation, and as regarded today, AhR has become an important factor in studies of immunomodulation. Besides immunological aspects, AhR also plays a role in pharmacological, toxicological and many other physiological processes such as adaptive metabolism. In recent years, epigenetic mechanisms have provided new insight into gene regulation and reveal a new contribution to autoimmune disease pathogenesis. DNA methylation, histone modifications, chromatin alterations, microRNA and consequently non-genetic changes in phenotypes connect with environmental factors. Increasing data reveals AhR cross-roads with the most significant in immunology pathways. Although study on epigenetic modulations in autoimmune diseases is still not well understood, therefore future research will help us understand their pathophysiology and help to find new therapeutic strategies. Present literature review sheds the light on the common ground between remodeling chromatin compounds and autoimmune antibodies used in diagnostics. In the proposed review we summarize recent findings that describe epigenetic factors which regulate AhR activity and impact diverse immunological responses and pathological changes. Full article

(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology 2.0)

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