Characterisation of a dendritic cell subset in synovial tissue which strongly expresses Jak/STAT transcription factors from patients with rheumatoid arthritis.
OBJECTIVE
To characterise the phenotype of the putative dendritic cells strongly expressing Jak3 and STAT4, which have been previously identified in the synovial tissue of patients with active rheumatoid arthritis (RA).


METHODS
Synovial biopsy specimens were obtained at arthroscopy from 30 patients with active RA (42 synovial biopsies). Immunohistological analysis was performed using monoclonal antibodies to detect dendritic cell subsets, including activation markers and cytokines relevant to dendritic cell function. Co-localisation of cell surface markers and cytokines was assessed primarily using sequential sections, with results confirmed by dual immunohistochemistry and immunofluorescence with confocal microscopy.


RESULTS
The dendritic cells identified in RA synovial tissue that strongly express Jak3 also strongly express STAT4 and STAT 6 and are correlated with the presence of serum rheumatoid factor. These cells are not confined to a single dendritic cell subset, with cells having phenotypes consistent with both myeloid- and plasmacytoid-type dendritic cells. The activation status of these dendritic cells suggests that they are maturing or mature dendritic cells. These dendritic cells produce IL12 as well as interferon alpha and gamma.


CONCLUSIONS
The close correlation of these dendritic cells with the presence of serum rheumatoid factor, a prognostic factor for worse disease outcome, and the strong expression by these cells of components of the Jak/STAT transcription factor pathway suggest a potential therapeutic target for the treatment of RA.
Walker
J G
JG
Repatriation General Hospital, Daws Rd, Daw Park, 5041 South Australia.
Ahern
M J
MJ
Coleman
M
M
Weedon
H
H
Papangelis
V
V
Beroukas
D
D
Roberts-Thomson
P J
PJ
Smith
M D
MD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000601:surgery; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D053616:Janus Kinase 3 / Q000378:metabolism*; D008213:Lymphocyte Activation; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000032:analysis; D050797:STAT4 Transcription Factor / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013583:Synovial Membrane / Q000276:immunology* / Q000378:metabolism
D015415:Biomarkers; D016898:Interferon-alpha; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D018664:Interleukin-12; D007371:Interferon-gamma; D002097:C-Reactive Protein; D012217:Rheumatoid Factor; D053616:Janus Kinase 3