Dendritic cells from patients with rheumatoid arthritis lack the interleukin 13 mediated increase of Fc gamma RII expression, which has clear functional consequences.
BACKGROUND
Dendritic cell (DC) function is largely tailored by Fc gamma receptors (Fc gamma R) and is critical for every immune response.


OBJECTIVE
To compare interleukin (IL) 13 mediated regulation of Fc gamma RII 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. F cgammaRI, 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 Fc gamma RII 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 Fc gamma R mediated triggering suggests that IL13 induces up regulation of specifically Fc gamma RII. 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 Fc gamma RII regulation was further substantiated by the finding that IL13 CDC increased antigen uptake capacity, whereas IL13 RADC did not.


CONCLUSIONS
IL13 regulates the expression of inhibitory Fc gamma RII in normal subjects but not in RA, potentially resulting in a chronic proinflammatory immune reaction in RA. Unravelling the underlying mechanisms of Fc gamma RII regulation might lead to new therapeutic targets in RA.
Radstake
T R D J
TR
Geert Grooteplein 8, 6500 HB Nijmegen, The Netherlands. T.Radstake@reuma.umcn.nl
Nabbe
K C A M
KC
Wenink
M H
MH
Roelofs
M F
MF
Oosterlaar
A
A
van Lieshout
A W T
AW
Barrera
P
P
van Lent
P L E M
PL
van den Berg
W B
WB
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D018793:Interleukin-13 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D016133:Polymerase Chain Reaction / Q000379:methods; D017452:Receptors, IgG / Q000097:blood*; D015398:Signal Transduction / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D018793:Interleukin-13; D017452:Receptors, IgG; D015847:Interleukin-4