The aryl hydrocarbon receptor is functionally upregulated early in the course of human <scp>T</scp>‐cell activation

Prigent, Laurie; Robineau, Marc; Jouneau, S.; Morzadec, Claudie; Louarn, Laetitia; Vernhet, Laurent; Fardel, Olivier; Sparfel, Lydie

doi:10.1002/eji.201343920

Cited by 33 publications

(49 citation statements)

References 35 publications

(44 reference statements)

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“…In this regard, a recent study showed that resting human blood T-cells (like those used in our study) were unable to over-express mRNA CYP1A1 when treated with AhR agonists; this suggested to us an inactive form of AhR. However, active T-cells are able to induce over-expression of mRNA CYP1A1 when treated with TCDD and benzo[a]pyrene, suggesting an active form of AhR (Prigent et al, 2014).…”

Section: Discussionsupporting

confidence: 44%

“…Also, an induction of the cytochromes P450 1A1 (CYP1A1) and 1B1 (CYP1B1) mRNA expression as AhR activation markers has been observed in blood cells (Prigent et al, 2014). Moreover, increasing experimental evidence supports an important role for AhR in the regulation of immune responses.…”

Section: Introductionmentioning

confidence: 95%

“…The AhR is mainly expressed in liver cells, but it is also present in blood cells (Prigent et al, 2014;Schote et al, 2007;Siest et al, 2008). Also, an induction of the cytochromes P450 1A1 (CYP1A1) and 1B1 (CYP1B1) mRNA expression as AhR activation markers has been observed in blood cells (Prigent et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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DDE and PCB 153 independently induce aryl hydrocarbon receptor (AhR) expression in peripheral blood mononuclear cells

Gaspar-Ramírez

Pérez‐Vázquez

Salgado‐Bustamante³

et al. 2014

Journal of Immunotoxicology

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Recent studies have demonstrated that compounds inducing pro-inflammatory cytokines enhance AhR expression. The aim of this study was 2-fold: (1) to determine if two pro-inflammatory compounds, dichlorodiphenyldichloroethylene (DDE) and 2,2 0 ,4,4 0 ,5,5 0 -hexa-chlorobiphenyl (PCB 153), independently affect AhR gene expression in peripheral blood mononuclear cells (PBMC); and (2) if affected, to determine whether the mechanism involved was due to AhR activation or to a pro-inflammatory effect of the chemicals. PBMC isolated from healthy individuals were incubated in the presence of DDE (10 mg/ml) and PCB 153 (20 ng/ml) over time and AhR and CYP1A1 expression was assessed with a real-time PCR technique. The results indicated there was over-expression of the AhR mRNA in PBMC when the cells were treated with DDE and PCB 153. No changes in expression levels of CYP1A1 mRNA were found. Importantly, when the cells were exposed to DDE and PCB 153 in the presence of an antagonist of tumor necrosis factor (TNF)-, the over-expression of AhR was abolished; as expected, the expression of CYP1A1 was unaffected. In conclusion, these studies demonstrated for the first time an increment of AhR expression ''in vitro'' in PBMC treated with two pro-inflammatory environmental pollutants, DDE and PCB153. Moreover, the over-expression of AhR was dependent of TNF induced by DDE and PCB 153 and was independent of AhR activation.

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Section: Discussionsupporting

confidence: 44%

Section: Introductionmentioning

confidence: 95%

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DDE and PCB 153 independently induce aryl hydrocarbon receptor (AhR) expression in peripheral blood mononuclear cells

Gaspar-Ramírez

Pérez‐Vázquez

Salgado‐Bustamante³

et al. 2014

Journal of Immunotoxicology

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“…These results imply target-specific effects of the AHR agonist FICZ for IL-22 and c-Kit. The expression of AHR in human T cell subsets was previously shown243940. Prigent et al .…”

Section: Discussionmentioning

confidence: 91%

“…Prigent et al . demonstrated an induction of AHR in Th cells during activation and differentiation39. The different expression levels of AHR in human Th cell subsets and different activation states of the cells might be crucial for the simultaneous induction of IL-22 and c-Kit.…”

Section: Discussionmentioning

confidence: 94%

Cytochrome P450s in human immune cells regulate IL-22 and c-Kit via an AHR feedback loop

Effner

Hiller

Eyerich

et al. 2017

Sci Rep

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The mechanisms how environmental compounds influence the human immune system are unknown. The environmentally sensitive transcription factor aryl hydrocarbon receptor (AHR) has immune-modulating functions and responds to small molecules. Cytochrome P4501 enzymes (CYP1) act downstream of the AHR and metabolize small molecules. However, it is currently unknown whether CYP1 activity is relevant for immune modulation. We studied the interdependence of CYP1 and AHR in human primary immune cells using pharmacological methods. CYP1 inhibition increased the expression levels of the stem cell factor receptor (c-Kit) and interleukin (IL)-22 but decreased IL-17. Single cell analyses showed that CYP1 inhibition especially promoted CD4+ helper T (Th) cells that co-express c-Kit and IL-22 simultaneously. The addition of an AHR antagonist reversed all these effects. In addition to T cells, we screened other human immune cells for CYP and found cell-specific fingerprints, suggesting that similar mechanisms are present in multiple immune cells. We describe a feedback loop yet unknown in human immune cells where CYP1 inhibition resulted in an altered AHR-dependent immune response. This mechanism relates CYP1-dependent metabolism of environmental small molecules to human immunity.

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Immunosenescence: an unexplored role in glomerulonephritis

2022

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Immunosenescence is a natural ageing phenomenon with alterations in innate and especially adaptive immunity and contributes to reduced antimicrobial defence and chronic low‐grade inflammation. This is mostly reflected by an increase in organ‐directed and/or circulating reactive and cytolytic terminally differentiated T cells that have lost their expression of the costimulatory receptor CD28. Apart from being induced by a genetic predisposition, ageing or viral infections (particularly cytomegalovirus infection), immunosenescence is accelerated in many inflammatory diseases and uraemia. This translates into an enhancement of vascular inflammation and cardiovascular disease varying from endothelial dysfunction to plaque rupture. Emerging data point to a mechanistic role of CD28null T cells in glomerulonephritis, where they initiate and propagate local inflammation in concordance with dendritic cells and macrophages. They are suitably equipped to escape immunological dampening by the absence of homing to lymph nodes, anti‐apoptotic properties and resistance to suppression by regulatory T cells. Early accumulation of senescent CD28null T cells precedes glomerular or vascular injury, and targeting these cells could open avenues for early treatment interventions that aim at abrogating a detrimental vicious cycle.

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The aryl hydrocarbon receptor is functionally upregulated early in the course of human T‐cell activation

Cited by 33 publications

References 35 publications

DDE and PCB 153 independently induce aryl hydrocarbon receptor (AhR) expression in peripheral blood mononuclear cells

DDE and PCB 153 independently induce aryl hydrocarbon receptor (AhR) expression in peripheral blood mononuclear cells

Cytochrome P450s in human immune cells regulate IL-22 and c-Kit via an AHR feedback loop

Immunosenescence: an unexplored role in glomerulonephritis

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