Synovial dendritic cells in juvenile idiopathic arthritis (JIA) express receptor activator of NF-kappaB (RANK).
OBJECTIVE
To analyse the expression of receptor activator of NF-kappaB (RANK) and RANK ligand (RANKL) in the joints of children with juvenile idiopathic arthritis (JIA), to characterize the phenotype of RANK(+) cells and to test the hypothesis that some RANK(+) cells are of the dendritic type.


METHODS
Paired samples of peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) from children with oligoarticular (n=14) or polyarticular (n=4) JIA and PBMC from 10 control subjects were studied for expression of RANK, RANKL and dendritic cell-specific ICAM (intercellular adhesion molecule)-grabbing non-integrin (DC-SIGN) by the reverse transcriptase-polymerase chain reaction and three-colour flow cytometry. Expression of DC-SIGN and RANK was followed after 1 week of culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4).


RESULTS
mRNA for RANK was detected in both adherent cells and T cells from PBMC and SFMC of patients with JIA and in control PBMC, while mRNA for RANKL was detectable in the T-cell fraction from JIA patients but not in that from controls. By flow cytometry, a large number of RANK(+) cells were detected in the joint; these cells had the phenotype HLA-DR(hi)CD86(hi) CD11c(+) and expressed low levels of DC-SIGN.


CONCLUSIONS
There is increased expression of RANKL and RANK in the juvenile arthritic joint. RANK is expressed on a population of cells with features of dendritic cells. RANK/RANKL interactions may contribute to the survival of inflammatory cells within the joint, as well as to erosions and osteoporosis in juvenile arthritis.
Varsani
H
H
Rheumatology Unit, Institute of Child Health, University College London, London, UK.
Patel
A
A
van Kooyk
Y
Y
Woo
P
P
Wedderburn
L R
LR
D000328:Adult; D001171:Arthritis, Juvenile / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D003713:Dendritic Cells / Q000378:metabolism*; D015870:Gene Expression; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000378:metabolism*
D002352:Carrier Proteins; D006023:Glycoproteins; D008024:Ligands; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human