Dendritic cells provide a potential link between smoking and inflammation in rheumatoid arthritisReport as inadecuate




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Arthritis Research and Therapy

, 14:R208

First Online: 04 October 2012Received: 27 April 2012Revised: 07 September 2012Accepted: 04 October 2012

Abstract

IntroductionSmoking increases the risk of developing rheumatoid arthritis RA and affects the severity of established RA. Smoking can impact on Th17 lymphocyte differentiation and function through activation of the aryl hydrocarbon receptor AHR, a process with implications for the pathogenic mechanisms in RA that involve the cytokine, interleukin IL-17A. The objective of this study was to establish any effect of smoking on the inflammatory tissue lesions of rheumatoid arthritis via the AHR and IL-17A.

MethodsTwenty synovial and eighteen subcutaneous nodule tissue samples from 31 patients with RA were studied. Patient smoking status at the time of tissue collection was established. Expression of AHR, CYP1A1, AHRR, IL6, IL17A, IL17F, IL22, IL23, IL23R, IFNG, TBX21, IDO1 and FOXP3 genes were assessed in tissues and cultured cells using real-time PCR. Two-colour immunofluorescence was used to co-localise AHR and CYP1A1 protein in synovial tissues. The response of monocytes and monocyte-derived dendritic cells mo-DCs to the AHR agonist, benzoapyrene BaP was compared in vitro.

ResultsAHR gene expression was demonstrated in rheumatoid synovial tissues and nodules with significantly greater expression in synovia. Expression was not influenced by smoking in either tissue. Evidence of AHR activation, indicated by CYP1A1 and AHRR gene expression, was found only in synovia from patients who smoked. However, IL17A gene expression was lower in synovia from smokers. TBX21 and FOXP3 expression was not affected by smoking. Within the synovial tissues of smokers the principal cell type with evidence of AHR activation was a subset of synovial DCs. This observation was consistent with the sensitivity of human mo-DCs to BaP stimulation demonstrated in vitro. Exposure to BaP affected mo-DC function as demonstrated by decreased IL6 expression induced by PolyI:C, without affecting indoleamine 2,3 dioxygenase IDO1 expression.

ConclusionOur findings show that one effect of smoking on inflamed rheumatoid synovial tissue involves activation of the AHR pathway. A subset of synovial DCs is important in the response to cigarette smoke. The potential for smoking to affect DC behaviour in joint tissues has relevance to both early and late phases of RA pathogenesis and warrants further investigation.

AbbreviationsACPAanticitrullinated peptide antibody

AHRaryl hydrocarbon receptor

AHRRAHR repressor

BαPbenzoapyrene

Ctthreshold cycle

CYPcytochrome P450

DMARDsdisease-modifying anti-rheumatic drugs

DMSOdimethylsulphoxide

GAPDHglyceraldehede-3-phosphate dehydrogenase

ILinterleukin

Mo-DCmonocyte-derived dendritic cell

OAosteoarthritis

PAHspolycyclic aromatic hydrocarbons

PBperipheral blood

PMAphorbol 12-myristate 13 acetate

Poly IC: polyinosinic:polycytidylic acid

RArheumatoid arthritis

RFrheumatoid factor

rhrecombinant human

RT-PCRreal-time polymerase chain reaction

GMCSFgranulocyte, macrophage colony stimulating factor

SEHLADRB1 shared eptiope

SEMstandard error of the mean

ThT-helper

TNFtumor necrosis factorα

XRExenobiotic response element.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4046 contains supplementary material, which is available to authorized users.

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Author: Marina G Kazantseva - John Highton - Lisa K Stamp - Paul A Hessian

Source: https://link.springer.com/







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