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

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

doi:10.3390/ijms22020757

Cited by 40 publications

(28 citation statements)

References 148 publications

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“…As there are several recent reviews excellently summarizing the role of AHR as a key regulatory molecule in the immune system [10][11][12][16][17][18], the impact of AHR on immune cells is only briefly discussed here.…”

Section: Ahr Immune Functionmentioning

confidence: 99%

The aryl hydrocarbon receptor in liver inflammation

Carambia

Schuran

2021

Semin Immunopathol

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The aryl hydrocarbon receptor (AHR) is a ubiquitously expressed ligand-activated transcription factor with multifaceted physiological functions. In the immune system, AHR has been unequivocally identified as a key regulatory factor that can integrate environmental, dietary, or microbial signals into innate and adaptive immune responses. Correspondingly, AHR activity seems to be most important at barrier organs, such as the gut, skin, and lung. The liver is likewise prominently exposed to gut-derived dietary or microbial AHR ligands and, moreover, generates plenty of AHR ligands itself. Yet, surprisingly little is known about the role of AHR in the regulation of hepatic immune responses, which are normally biased towards tolerance, preventing harmful inflammation in response to innocuous stimuli. In this review, we summarize the current knowledge about the role of AHR in hepatic immune responses in the healthy liver as well as in inflammatory liver disease. Moreover, we discuss AHR as a potential therapeutic target in hepatic disorders, including autoimmune liver disease, liver fibrosis, and liver cancer.

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Section: Ahr Immune Functionmentioning

confidence: 99%

The aryl hydrocarbon receptor in liver inflammation

Carambia

Schuran

2021

Semin Immunopathol

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“…Aryl Hydrocarbon Receptor (AhR), a ligand-dependent transcription factor, is known to mediate the biochemical and toxic effects of xenobiotics, environmental stresses, endogenous ligands, microbial-derived products, and physiological compounds such as tryptophan derivatives [ 1 , 2 , 3 , 4 , 5 ]. Recent data indicate that AhR is implicated in several physiological processes such as xenobiotic metabolism, cell cycle regulation, reproduction, development, and immune response, by playing a pivotal role in signaling networks [ 5 , 6 , 7 ]. Moreover, AhR involvement has been described in the pathogenesis of different diseases [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Aryl Hydrocarbon Receptor Activation in Inflammatory Chronic Skin Diseases

Napolitano

Fabbrocini

Picone

et al. 2021

Cells

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Aryl Hydrocarbon Receptor (AhR) is an evolutionary transcription factor which acts as a crucial sensor of different exogenous and endogenous molecules Recent data indicate that AhR is implicated in several physiological processes such as cell physiology, host defense, proliferation and differentiation of immune cells, and detoxification. Moreover, AhR involvement has been reported in the development and maintenance of several pathological conditions. In recent years, an increasing number of studies have accumulated highlighting the regulatory role of AhR in the physiology of the skin. However, there is evidence of both beneficial and harmful effects of AHR signaling. At present, most of the evidence concerns inflammatory skin diseases, in particular atopic dermatitis, psoriasis, acne, and hidradenitis suppurativa. This review exam-ines the role of AhR in skin homeostasis and the therapeutic implication of its pharmacological modulation in these cutaneous inflammatory diseases.

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“…If the pioneer factor were transiently expressed in retinal progenitor cells (as observed for Ascl1 and Sox2, but not Isl1; STable 12), rendering chromatin accessible to activator TF that are expressed and operate in later stages of development, this may conceivably also generate the observed depletion of binding motifs in the ATAC-Seq peaks of genes that are overexpressed in the same cell type as the pioneer TF. We note that three of the TF in the list of putative repressors (Ahr, Hif1α and Clock), which are typically regarded as paradigmatic activators, are functionally connected: Ahr competes with Hif1α for binding to the nuclear translocator protein Arnt and -possibly -with Clock for binding to Arnt-similar Bmal1 [65]. It is tempting to speculate that this connection may underpin the fact that these three supposedly activator TF appear as repressors in our analyses.…”

Section: E Fmentioning

confidence: 72%

Evidence from combined analysis of single cell RNA-Seq and ATAC-Seq data of regulatory toggles operating in native and iPS-derived murine retina

Georges

Lavergne

Mandai³

et al. 2020

Preprint

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17We herein report the generation and analysis of single-cell RNA Seq data (> 38,000 cells) from 18 native and iPSC-derived murine retina at four matched developmental stages spanning the 19 emergence of the major retinal cell types. We combine information from temporal sampling, 20 visualization of 3D UMAP manifolds in virtual reality, and RNA velocity analysis to show that 21 iPSC-derived 3D retinal aggregates broadly recapitulate the native developmental trajectories 22 with evidence supporting re-specification from amacrine cells to horizontal and 23 photoreceptor precursor cells, as well as a direct differentiation of Tbr1 + retinal ganglion cells 24 from neuro-epithelium cells. We show relaxation of spatial and temporal transcriptome 25 control, premature emergence and dominance of photoreceptor precursor cells, and 26 susceptibility of dynamically regulated pathways and transcription factors to culture 27 conditions in iPSC-derived retina. We generate bulk ATAC-Seq data for native and iPSC-28 derived murine retina at three of the four same developmental stages identifying ~125,000 29 peaks. The number of ATAC-Seq peaks increased with developmental stage in native but not 30 in iPSC-derived retina. We combine single-cell RNA Seq with ATAC-Seq information and 31demonstrate that approximately halve of the transcription factors that are dynamically 32 Georges et al.Page 2 of 46 regulated during retinal development act as repressors rather than activators. We provide 33 evidence that sets of activators and repressors with cell-type specific expression control 34

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

Cited by 40 publications

References 148 publications

The aryl hydrocarbon receptor in liver inflammation

The aryl hydrocarbon receptor in liver inflammation

Role of Aryl Hydrocarbon Receptor Activation in Inflammatory Chronic Skin Diseases

Evidence from combined analysis of single cell RNA-Seq and ATAC-Seq data of regulatory toggles operating in native and iPS-derived murine retina

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