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Cellular and Molecular Life Sciences

, Volume 73, Issue 1, pp 95–117 | Cite as

The emerging role of aryl hydrocarbon receptor in the activation and differentiation of Th17 cells

  • Eszter Baricza
  • Viola Tamási
  • Nikolett Marton
  • Edit I. Buzás
  • György NagyEmail author
Review

Abstract

The aryl hydrocarbon receptor (AHR) is a cytoplasmic transcription factor, which plays an essential role in the xenobiotic metabolism in a wide variety of cells. The AHR gene is evolutionarily conserved and it has a central role not only in the differentiation and maturation of many tissues, but also in the toxicological metabolism of the cell by the activation of metabolizing enzymes. Several lines of evidence support that both AHR agonists and antagonists have profound immunological effects; and recently, the AHR has been implicated in antibacterial host defense. According to recent studies, the AHR is essential for the differentiation and activation of T helper 17 (Th17) cells. It is well known that Th17 cells have a central role in the development of inflammation, which is crucial in the defense against pathogens. In addition, Th17 cells play a major role in the pathogenesis of several autoimmune diseases such as rheumatoid arthritis. Therefore, the AHR may provide connection between the environmental chemicals, the immune regulation, and autoimmunity. In the present review, we summarize the role of the AHR in the Th17 cell functions.

Keywords

Aryl hydrocarbon receptor Th17 cell Polycyclic aromatic hydrocarbons RAR-related orphan nuclear receptor gamma t 

Abbreviations

3-HK

3-Hydroxykynurenine

3-MC

3-Methylcholanthrene

AHR

Aryl hydrocarbon receptor

AHRR

Nuclear AHR repressor

AR

Androgen receptor

ARNT

Aryl hydrocarbon receptor nuclear translocator

B[a]P

Benzo[alpha]pyrene

BBB-ECs

Blood–brain barrier endothelial cells

BD

Bechet’s disease

bHLH/PAS

Basic helix–loop–helix/Per–Arnt–Sim

CBP/P300

CREB-binding protein/E1A binding protein p300 protein

CCL20

Chemokine (C–C motif) ligand 20

CCR6

Chemokine receptor 6

CH-223191

2-Methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide

c-MAF

V-Maf avian musculoaponeuroticfibrosarcoma oncogene homolog

CNS

Central nervous system

CXCL1

Chemokine (C-X-C motif) ligand 1

CYP1A1

Cytochrome P450, family 1, subfamily A, polypeptide 1

DCs

Dendritic cells

DIM

3,3′-Diindolylmethane

E2

17β-Estradiol

EAE

Experimental autoimmune encephalomyelitis

eNOS

Endothelial NO synthase

ER

Estrogen receptor

ERE

Estrogen response element

ERα

Estrogen receptor alpha

FICZ

6-Formylindolo(3,2-b)carbazole

FoxP3

Forkhead box P3

FKF

Formylkynurenineformamidase

G-CSM

Granulocyte colony-stimulating factor

GM-CSF

Granulocyte–monocyte colony-stimulating factor

HAHs

Halogenated-dioxins and their congeners

HSP90

Heat shock protein 90

I3C

Indole-3-carbinol

I3S

Indoxyl 3-sulfate

IBD

Inflammatory bowel disease

IDO1

2,3-Dioxygenase 1

IDO2

2,3-Dioxygenase 2

IFNγ

Interferon gamma

ILC

Innate lymphoid cell

ILFs

Isolated lymphoid follicles

IELs

Intraepithelial lymphocytes

LTi

Lymphoid tissue inducer

IL-10

Interleukin 10

IL-1β

Interleukin-1 beta

ITE

2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester

KATs

Kynurenine aminotransferases

KLRB1

Killer cell lectin-like receptor B1

KMO

Kynurenine 3-monooxygenase

KYN

Kynurenine

KYNA

Kynurenic acid

LXR

Liver X receptor

LXRα

Liver X receptor alpha

LXRβ

Liver X receptor beta

MMP

Matrix metalloproteinase

MDR1

Multidrug resistance protein 1

MS

Multiple sclerosis

NES

Nuclear export signal

NF-1

Nuclear factor 1

NFκB

Nuclear factor kappa-light-chain-enhancer of activated B cells

NK

Natural killer

NKT

Natural killer T

NO

Nitric oxide

p23

Prostaglandin E synthase 3

PAHs

Polycyclic aromatic hydrocarbons

PAS

PerArntSim

PBMCs

Peripherial blood mononuclear cells

PCBs

Planar polychlorinated biphenyls

POLY

Polydatin

PolylC

Toll-like receptor agonist polyinosinic:polycytidylic acid

PPARs

Peroxisome proliferator-activated receptors

PPARα

Peroxisome proliferator-activated receptor alpha

PPRE

PPAR response element

RA

Rheumatoid arthritis

RES

Resveratrol

RORC2

Retinoic acid-related orphan receptor variant 2

RORγt

RAR-related orphan nuclear receptor gamma t

SE

Shared epitope

SLE

Systemic lupus erythematosus

SOCS3

Suppressor of cytokine signaling 3

Srebp-1

Sterol regulatory element-binding protein 1

TAD

Transactivation domain

T-bet

T-box expressed in T cells

TBP

TATA-box-binding protein

TDO

Tryptophan 2,3-dioxygenase

TGFB1

Tumor growth factor beta 1

Th17

T helper 17

Th17(23)

IL-23 induced Th17 cells

Th17(β)

Conventional Th17 cells

TNBS

2,4,6-Trinitrobenzenesulfonic acid

TNFα

Tumor necrosis factor alpha

Tr1

Type 1 regulatory T

Treg

Regulatory T cell

UGT1A1

UDP glucuronosyltransferase 1 family, polypeptide A1

XAP2

Hepatitis B virus X-associated protein

XREs

Xenobiotic responsive elements

WY

WY-14643

α-NF

Alpha-napthoflavone

γδ T

Gamma delta T cells

Notes

Acknowledgments

The study was supported by the Hungarian Scientific Research Fund (Grant: OTKA-PD 108297, OTKA-NN 111023 and NK84043and K111958, MEDINPROT, FP7 COST ME HAD BM1202 and FP7 Marie Curie ITN “DYNANO”).

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Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Eszter Baricza
    • 1
  • Viola Tamási
    • 1
  • Nikolett Marton
    • 1
  • Edit I. Buzás
    • 1
  • György Nagy
    • 1
    • 2
    Email author
  1. 1.Department of Genetics, Cell and ImmunobiologySemmelweis UniversityBudapestHungary
  2. 2.Department of RheumatologySemmelweis UniversityBudapestHungary

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