Aryl Hydrocarbon Receptor–Dependent Pathways in Immune Regulation

Gargaro, Marco; Pirro, Matteo; Romani, Rita; Zelante, Teresa; Fallarino, Francesca

doi:10.1111/ajt.13716

Cited by 20 publications

(18 citation statements)

References 43 publications

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“…Presumably altered regulation of CYP1A impacts on the ability to detoxify other contaminants, and altered binding affinity of AHR2 to dioxin-like compounds may also impact binding of the endogenous ligand(s). Studies in humans and mice ( Mus musculus ) have shown that the AHR gene is important for immune system functioning [67,68], suggesting potential immune-related costs of these adaptations. Interestingly, F. heteroclitus populations resistant to PAH exposure differ in their immune function and susceptibility to disease (e.g.…”

Section: Physiological Mechanisms For Adaptations and Their Potentialmentioning

confidence: 99%

Adaptive capabilities and fitness consequences associated with pollution exposure in fish

Hamilton

Rolshausen

Webster

et al. 2017

Phil. Trans. R. Soc. B

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Many fish populations are exposed to harmful levels of chemical pollution and selection pressures associated with these exposures have led to the evolution of tolerance. Our understanding of the physiological basis for these adaptations is limited, but they are likely to include processes involved with the absorption, distribution, metabolism and/or excretion of the target chemical. Other potential adaptive mechanisms include enhancements in antioxidant responses, an increased capacity for DNA and/or tissue repair and alterations to the life cycle of fish that enable earlier reproduction. Analysis of single-nucleotide polymorphism frequencies has shown that tolerance to hydrocarbon pollutants in both marine and estuarine fish species involves alteration in the expression of the xenobiotic metabolism enzyme CYP1A. In this review, we present novel data showing also that variants of the CYP1A gene have been under selection in guppies living in Trinidadian rivers heavily polluted with crude oil. Potential costs associated with these adaptations could reduce fitness in unpolluted water conditions. Integrating knowledge of local adaptation to pollution is an important future consideration in conservation practices such as for successful restocking, and improving connectivity within river systems.This article is part of the themed issue ‘Human influences on evolution, and the ecological and societal consequences’.

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Section: Physiological Mechanisms For Adaptations and Their Potentialmentioning

confidence: 99%

Adaptive capabilities and fitness consequences associated with pollution exposure in fish

Hamilton

Rolshausen

Webster

et al. 2017

Phil. Trans. R. Soc. B

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“…Some microbiome-associated metabolites are bioactive and affect the host cellular processes including differentiation, migration, proliferation, and apoptosis, thereby featuring pleotropic physiological or pathophysiological effects on the eukaryotic host. A number of metabolites impact mucosal and systemic immune maturation and function, in steady state and during disease (4)(5)(6)(7)(8). The host has evolved multiple metabolite sensing platforms, and downstream immune signaling pathways that confer reactivity to microbiome-modulated metabolites (9,10).…”

mentioning

confidence: 99%

Microbiome-Modulated Metabolites at the Interface of Host Immunity

Blacher

Levy

Tatirovsky

et al. 2017

The Journal of Immunology

278

213

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The mammalian gastrointestinal tract and associated mucosal immune system harbor a large repertoire of metabolites of prokaryotic and eukaryotic origin that play important roles in eukaryotic development and physiology. These often bioactive small molecules originate from nutrition- and environmental-related sources, or are endogenously produced and modulated by the host and its microbiota. A complex network of interactions exists between the intestinal mucosal immune system and the microbiota. This intimate cross-talk may be driven by metabolite secretion and signaling, and features profound influences on host immunity and physiology, including the endocrine, metabolic, and nervous system function in health and disease. Alterations in microbiome-associated metabolite levels and activity are implicated in the pathogenesis of a growing number of illnesses. In this review we discuss the origin and influence of microbiome-modulated metabolites, with an emphasis on immune cell development and function. We further highlight the emerging data potentially implicating metabolite misbalance with host-microbiome-associated disease.

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“…Our previous work showed that calcitriol reduces expression of the aryl hydrocarbon receptor (AhR) [3]. AhR plays a pivotal role in the differentiation of multiple CD4 T cell subsets including Th17, Th9, and Tregs [12]. If LCA treatment functions in a manner similar to calcitriol, then we predict that LCA also reduces protein expression of AhR.…”

Section: Lca Mediated Reduction Of Ahrmentioning

confidence: 90%

A microbial metabolite, Lithocholic acid, suppresses IFN-γ and AhR expression by human cord blood CD4 T cells

Iwashima

2018

Preprint

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Declarations of interest: none Highlights• Lithocholic acid suppresses IFNγ production by CD4 T cells.• Lithocholic acid suppresses STAT1 and IRF1 expression by activated CD4 T cells.• Lithocholic acid suppresses AhR in a comparable manner to calcitriol. AbstractVitamin D is a well-known micronutrient that modulates immune responses by epigenetic and transcriptional regulation of target genes, such as inflammatory cytokines. Our group recently demonstrated that the most active form of vitamin D, calcitriol, reduces expression of a transcription factor known as the aryl hydrocarbon receptor (AhR) and inhibits differentiation of a pro-inflammatory T cell subset, Th9. Lithocholic acid (LCA), a secondary bile acid produced by commensal bacteria, is known to bind to and activate the vitamin D receptor (VDR) in a manner comparable to calcitriol. In this study, Naïve CD4 T cells were isolated from healthy human umbilical mononuclear cells and were stimulated in the presence or absence of LCA. We determined the effect of LCA on human cord blood T cell activation by measuring IFN-γ production and protein expression of IFN-γ receptor-mediated signaling molecules. We found that LCA reduces production of IFN-γ and decreases phosphorylation of STAT1 as well as expression of AhR, STAT1, and IRF1 by activated human cord blood CD4 T cells.LCA inhibits expression of IFN-g and reduces its receptor signaling molecules.

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Aryl Hydrocarbon Receptor–Dependent Pathways in Immune Regulation

Cited by 20 publications

References 43 publications

Adaptive capabilities and fitness consequences associated with pollution exposure in fish

Adaptive capabilities and fitness consequences associated with pollution exposure in fish

Microbiome-Modulated Metabolites at the Interface of Host Immunity

A microbial metabolite, Lithocholic acid, suppresses IFN-γ and AhR expression by human cord blood CD4 T cells

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