RESEARCH - Increased expression of CCL18, CCL19, and CCL17 by dendritic cells from patients with RA and regulation by Fc gamma receptors

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Ann Rheum Dis. 2004 Aug 26 [Epub ahead of print]

Increased expression of CCL18, CCL19, and CCL17 by dendritic cells from

patients with rheumatoid arthritis and regulation by Fc gamma receptors.

Radstake TR, Van Der Voort R, Ten Brummelhuis M, De Waal Malefijt M,

Schreurs W, Looman M, Sloetjes A, Figdor CG, Van Den Berg WB, Barrera P,

Adema GJ.

UMC Nijmegen, The Netherlands.

OBJECTIVE: Dendritic cells (DC) play an essential role in the regulation

of both immunity and tolerance. DC orchestrate the attraction of

inflammatory cells by the production of various chemokines (CK).

Recently, It was suggested that Fc gamma receptors (Fc & [gamma]R) are

involved in the regulation of DC function. The aim of the study was to

assess the expression of a panel of CK by immature (iDC) and mature DC

(mDC) and its regulation by FcgammaR both in RA patients and healthy

donors (HC). METHODS: The expression CK by DC from RA patients and HC

was determined using Real Time quantitative PCR and ELISA techniques. DC

were derived from monocytes following standardized protocols. To study

the potential regulation by FcgammaR, iDC were stimulated with

immunecomplexes (IC) during LPS-induced maturation. The presence of CK

was studied in synovial tissue from patients with RA, OA and healthy

individuals by using RT- PCR techniques and immunohistochemistry.

RESULTS: iDC from RA patients show markedly increased mRNA levels of the

CK CCL18 and CXCL8. Upon maturation with LPS, the expression of CCL18,

CCL19, CXCL8, CCL3 and CCL17 increased dramatically and reached

significantly higher levels in RA patients. Monocytes failed to express

these CK. IC mediated triggering of the FcgammaR on DC from RA patients

with high disease activity resulted in a downregulation of all CK,

whereas the opposite effect was seen upon stimulation of DC from RA

patients with low disease activity and healthy donors. Moreover, CCL18,

CCL19, CCL17 and CXCL8 are significantly increased in the RA synovial

tissue.

CONCLUSION: In this study we provide evidence for elevated CK expression

levels by DC in RA patients. The expression of these CK is, at least

partly regulated by FcgammaR triggering. These data suggest a potential

role for CK producing DC in RA pathogenesis.

PMID: 15331393

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5331393 & dopt=Abstract

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