Aryl hydrocarbon receptor: Linking environment to immunity

Cella, Marina; Colonna, Marco

doi:10.1016/j.smim.2015.10.002

Cited by 103 publications

(111 citation statements)

References 80 publications

(94 reference statements)

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“…Aryl hydroxylase (AhR) the transcription factor of CYP1A1 is also associated with immunosuppression after activation of IL-22 pathway, and the maintenance of intraepithelial in innate lymphocytes leading to the mucosal protection from inflammation [45].…”

Section: Catechoestrogens and Cytochrome P450 (Cyp1a1)mentioning

confidence: 99%

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

Matos¹,

Silva²,

Medeiros³

et al. 2018

Cervical Cancer - Screening, Treatment and Prevention - Universal Protocols for Ultimate Control

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Current knowledge point to persistence of risk factors for the development of cervical intraepithelial neoplasia. The infection with a high-risk oncogenic Human Papillomavirus (HPV) subtypes, most commonly 16 and 18, is a necessary, although not sufficient, condition for development of invasive cervical cancer (ICC) and its precancerous precursor, cervical intra-epithelial neoplasia (CIN). It has been suggested that CIN disease severity and the diversity of vaginal microbiota are associated and this may determine viral persistence and disease behaviour. Our work focuses on the genetic variability associated to the modulation of genotoxicity induced by vaginal microbiota diversity. Relatively little is known about the mechanisms associated with clearance or persistence of HPV infection, therefore we hypothesized that may be under the influence of the genetic background.

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Section: Catechoestrogens and Cytochrome P450 (Cyp1a1)mentioning

confidence: 99%

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

Matos¹,

Silva²,

Medeiros³

et al. 2018

Cervical Cancer - Screening, Treatment and Prevention - Universal Protocols for Ultimate Control

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“…Recently, a paradigm shift has occurred with the understanding that AhR has endogenous roles and is an important regulator of cell development, differentiation, and function (40). AhR is an important regulator of the development and function of both innate and adaptive immune cells, mediated by the ability of AhR to respond to endogenous ligands generated from the host cell, diet, and microbiota (41)(42)(43)(44). This recent paradigm shift has opened new avenues of research in the possibility of targeting AhR to treat inflammatory diseases in which a role of AhR has been found, including lupus (45) and colitis (46).…”

Section: Foxp3mentioning

confidence: 99%

Laquinimod arrests experimental autoimmune encephalomyelitis by activating the aryl hydrocarbon receptor

Kaye

Piryatinsky

Birnberg

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

118

102

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Laquinimod is an oral drug currently being evaluated for the treatment of relapsing, remitting, and primary progressive multiple sclerosis and Huntington's disease. Laquinimod exerts beneficial activities on both the peripheral immune system and the CNS with distinctive changes in CNS resident cell populations, especially astrocytes and microglia. Analysis of genome-wide expression data revealed activation of the aryl hydrocarbon receptor (AhR) pathway in laquinimod-treated mice. The AhR pathway modulates the differentiation and function of several cell populations, many of which play an important role in neuroinflammation. We therefore tested the consequences of AhR activation in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) using AhR knockout mice. We demonstrate that the pronounced effect of laquinimod on clinical score, CNS inflammation, and demyelination in EAE was abolished in AhR −/− mice. Furthermore, using bone marrow chimeras we show that deletion of AhR in the immune system fully abrogates, whereas deletion within the CNS partially abrogates the effect of laquinimod in EAE. These data strongly support the idea that AhR is necessary for the efficacy of laquinimod in EAE and that laquinimod may represent a first-in-class drug targeting AhR for the treatment of multiple sclerosis and other neurodegenerative diseases.aryl hydrocarbon receptor | EAE | laquinimod L aquinimod is an oral drug that is currently in late-stage clinical development for the treatment of relapsing remitting multiple sclerosis (RRMS), primary progressive MS, and Huntington's disease. Current knowledge indicates that laquinimod exerts activities both on the peripheral immune system and within the CNS. Laquinimod, at the 0.6-mg/d dose, has demonstrated efficacy in phase II and III MS clinical trials, in which it reduced relapse rate, disability progression, development of new and active MRI lesions, and brain atrophy (1-3). The clinical efficacy profile of laquinimod is characterized by a dissociation of the moderate magnitude of the effect on relapse reduction and its associated inflammatory MRI findings and the disproportionally large effect on disability progression. Such an efficacy profile in patients with RRMS may relate to a distinctive intracerebral activity potentially mediated via changes in CNS resident cell populations, potentially astrocytes and microglia.

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“…The transcription factor AHR has been reported to regulate IL-22 production in both T-cells and ILC3s36. We thus investigated whether AHR contributes to PGE 2 -cAMP signaling-dependent increase in adaptive IL-22 production.…”

Section: Resultsmentioning

confidence: 96%

“…This effect is mediated by cAMP-protein kinase A (PKA) signaling and induction of aryl hydrocarbon receptor (AHR), a transcription factor critical for both adaptive and innate IL-22 expression36. T-cell specific EP4 deficiency diminishes hapten-induced IL-22-expressing T cells in skin-draining lymph nodes (LNs).…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin E2 stimulates adaptive IL-22 production and promotes allergic contact dermatitis

Robb

McSorley

Lee

et al. 2018

Journal of Allergy and Clinical Immunology

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Background Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are both forms of eczema and are common inflammatory skin diseases with a central role of Th22-derived IL-22 in their pathogenesis. Although prostaglandin E2 (PGE2) is known to promote inflammation, little is known about its role in processes related to AD and ACD development, including IL-22 up-regulation. Objectives To investigate whether PGE2 has a role in IL-22 induction and development of ACD, which has increased prevalence in patients with AD. Methods T-cell cultures and in vivo sensitization of mice with haptens were used to assess the role of PGE2 in production of IL-22. The involvement of PGE2 receptors and their downstream signals were also examined. The effects of PGE2 were evaluated using the oxazolone (OXA)-induced ACD mouse model. The relationship of PGE2 and IL-22 signaling pathways in skin inflammation were also investigated using genomic profiling in human lesional AD skin. Results PGE2 induces IL-22 from T cells through its receptors EP2 and EP4 and involves cyclic adenosine monophosphate (cAMP) signaling. Selective deletion of EP4 in T-cells prevents hapten-induced IL-22 production in vivo, and inhibition of PGE2 synthesis limits atopic-like skin inflammation in the OXA-induced ACD model. Moreover, both PGE2 and IL-22 pathway genes were coordinately up-regulated in human AD lesional skin, but were below significant detection levels after corticosteroid or ultraviolet band B (UVB) treatments. Conclusions Our results define a crucial role for PGE2 in promoting ACD by facilitating IL-22 production from T-cells.

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Aryl hydrocarbon receptor: Linking environment to immunity

Cited by 103 publications

References 80 publications

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

Laquinimod arrests experimental autoimmune encephalomyelitis by activating the aryl hydrocarbon receptor

Prostaglandin E2 stimulates adaptive IL-22 production and promotes allergic contact dermatitis

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