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Environmental Exposition to Aromatic Hydrocarbon Receptor Ligands Modulates the CD4+ T Lymphocyte Subpopulations Profile

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Abstract

The aromatic hydrocarbon receptor (AhR) had been described as a molecular sensor to which many environmental pollutants, such as polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) binds leading to many biological and toxic effects. Recently, it had been demonstrated that the differentiation of CD4+ T cells is influenced by AhR ligands present in the surrounding microenvironment of the cells. In this study, we assessed the immune environment of CD4+ T cells in a cohort of firefighters, a group of individuals more exposed to AhR ligands. Our results showed that in firefighters, Th17 and Treg cells were increased compared to our control group. Also, the microenvironment presents an increase in cytokines promoting the differentiation of these cells in firefighters. The presence of a large number of AhR ligands in the firefighters' sera had been observed. Finally, in vitro treatments of CD4+ T cells with AhR ligands (BaP and Kynurenine) had shown an ability to modulate Treg and Th17 cells' differentiation.

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Abbreviations

AhR:

Aryl hydrocarbon receptor

AhRR:

Aryl hydrocarbon receptor repressor

ALD:

Alcohol dehydrogenase

APC:

Antigen-presenting cell

ARNT:

Aryl hydrocarbon receptor nuclear translocator

BaP:

Benzo(a)pyrene

BATF:

Basic leucine zipper transcription factor, ATF-like

bHLH–PAS:

Basic helix-loop-helix Per-ARNT-Sim

Bili:

Bilirubin

CARS:

Compensatory anti-inflammatory response syndrome

MHC:

Major histocompatibility complex

CYP450:

Cytochrome P450

DMBA:

7,12-Dimethylbenz(a)anthracene

DRE:

Dioxin response element

EGFR:

Epidermal growth factor receptor

FBS:

Fetal bovine serum

FICZ:

6-Formylindolo[3,2-b]carbazole

Foxp3:

Forkhead box P3

GATA-3:

GATA-3 binding protein

GST:

Glutathione S-transferase

GVH:

Graft versus host

HAH:

Halogenated aromatic hydrocarbon

PAH:

Polycyclic aromatic hydrocarbon

Hsp90:

Heat shock protein 90

I3C:

Indole-3-carbinol

IFNγ:

Interferon gamma

IL:

Interleukin

IRF4:

Interferon regulatory factor 4

Kyn:

Kynurenine

KMO:

Kynurenine 3-monooxygenase

LT:

T lymphocyte

MODS:

Multiple organ dysfunction syndrome

NES:

Nuclear export signal

NF-κB:

Nuclear factor-kappa B

NK:

Natural killer

NLS:

Nuclear localization signal

NQO:

NADH-quinone oxidoreductase

PBMC:

Peripheral blood mononuclear cells

RORγt:

RAR-related orphan receptor gamma

SIRS:

Systemic inflammatory response syndrome

T-bet:

T-box transcription factor

TAD:

Trans-activating domain

Tc:

Cytotoxic T cell

TCDD:

2,3,7,8-Tétrachlorodibenzo-p-dioxin

TGFβ:

Transforming growth factor beta

Th:

T helper cell

TNF:

Tumor necrosis factor

Treg:

Regulatory T cell

UGT:

Urdine triphosphate glucuronosyl transférase

VAF347:

(4-(3-Chloro-phenyl)-pyrimidin-2-yl)-(4-trifluoromethyl-phenyl)-amine

XRE:

Xenobiotic response element

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Acknowledgements

The authors would like to thank the volunteers who participated in this study as well as nurse Alexandre Arsenault.

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Contributions

JB conceived the study; GR, DL, and JB designed the study; GR and DL performed the experiments; GR, DL, and JB analyzed, interpreted the data, and wrote the paper; JB supervised the study.

Corresponding author

Correspondence to Jacques Bernier.

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The authors declare no conflicts of interest.

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Ricaud, G., Lim, D. & Bernier, J. Environmental Exposition to Aromatic Hydrocarbon Receptor Ligands Modulates the CD4+ T Lymphocyte Subpopulations Profile. Expo Health 13, 307–322 (2021). https://doi.org/10.1007/s12403-021-00385-w

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  • DOI: https://doi.org/10.1007/s12403-021-00385-w

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