PT  - JOURNAL ARTICLE
AU  - T R D J Radstake
AU  - K C A M Nabbe
AU  - M H Wenink
AU  - M F Roelofs
AU  - A Oosterlaar
AU  - A W T van Lieshout
AU  - P Barrera
AU  - P L E M van Lent
AU  - W B van den Berg
TI  - Dendritic cells from patients with rheumatoid arthritis lack the interleukin 13 mediated increase of FcγRII expression, which has clear functional consequences
AID  - 10.1136/ard.2004.034405
DP  - 2005 Dec 01
TA  - Annals of the Rheumatic Diseases
PG  - 1737--1743
VI  - 64
IP  - 12
4099  - http://ard.bmj.com/content/64/12/1737.short
4100  - http://ard.bmj.com/content/64/12/1737.full
SO  - Ann Rheum Dis2005 Dec 01; 64
AB  - Background: Dendritic cell (DC) function is largely tailored by Fc gamma receptors (FcγR) and is critical for every immune response.Objective: To compare interleukin (IL) 13 mediated regulation of FcγRII and its related DC function between healthy controls and patients with rheumatoid arthritis (RA).Methods: DC were derived from peripheral blood mononuclear cells according to standardised protocols. FcγRI, II, and III expression and DC phenotype were assessed by FACS analysis. The level of cytokine production and chemokine expression was measured by Luminex and real time quantitative polymerase chain reaction techniques. Antigen uptake capacity was studied by DC fluorescent heat aggregated immunoglobulins and FACS analysis.Results: Replacement of IL4 by IL13 clearly increased the expression of FcγRII on DC from healthy controls (CDC), but had no effect on DC from patients with RA (RADC). The lower production of inflammatory mediators by IL13 CDC upon FcγR mediated triggering suggests that IL13 induces up regulation of specifically FcγRII. RADC co-cultured with IL4 already displayed an inhibitory DC phenotype, but this inhibitory phenotype was not augmented by the addition of IL13. The defective FcγRII regulation was further substantiated by the finding that IL13 CDC increased antigen uptake capacity, whereas IL13 RADC did not.Conclusion: IL13 regulates the expression of inhibitory FcγRII in normal subjects but not in RA, potentially resulting in a chronic proinflammatory immune reaction in RA. Unravelling the underlying mechanisms of FcγRII regulation might lead to new therapeutic targets in RA.