Distinct expression pattern of IFN-alpha and TNF-alpha in juvenile idiopathic arthritis synovial tissue.
OBJECTIVE
Recent laboratory and clinical data suggest that two prototype autoimmune diseases, systemic lupus erythematosus and rheumatoid arthritis are mainly driven by distinct cytokines, interferon (IFN)-alpha and tumour necrosis factor (TNF)-alpha, respectively. We here investigated the presence and characteristics of natural type I IFN-producing cells (IPCs), as well as IFN-alpha and TNF-alpha expression at sites of inflammation in juvenile idiopathic arthritis (JIA).


METHODS
Peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MNCs) (n = 25 each) from JIA patients with active disease were studied. IPCs were identified as BCDA-2(+)CD123(+)HLA-DR(+)CD45RA(+) cells, and dendritic cells (DCs) as CD11c(+)CD14(-/low)lin(-) cells by flow cytometry. IPCs and DCs were analysed for Toll-like receptor-7 and -9 mRNA expression by real-time polymerase chain reaction. IFN-alpha was measured by enzyme-linked immunosorbent assay in serum, SF and in supernatants of influenza virus-infected, cultured IPCs. Synovial tissues of n = 6 additional JIA patients were analysed by immunohistochemistry using mAbs against CD123, IFN-alpha, TNF-alpha, CD3, CD19 and CD138.


RESULTS
IPCs were enriched in SF MNCs compared with PB MNCs in all JIA patients. Influenza-induced, but no spontaneous IFN-alpha release was detected from SF IPCs, and serum and SF IFN-alpha levels were not elevated. Nonetheless, in synovial tissue IFN-alpha producing cells accumulated at inflammatory lymph-follicular-like structures, while TNF-alpha producing cells were mostly found at the lining and sublining layers.


CONCLUSIONS
These data suggest that besides TNF-alpha-expressing cells, IFN-alpha-producing IPCs are involved in initiation, maintenance or regulation of the inflammatory response in JIA.
Gattorno
M
M
Second Division of Pediatrics, G. Gaslini Institute and University of Genoa, Largo G. Gaslini 5, 16147, Genoa, Italy. marcogattorno@ospedale-gaslini.ge.it
Chicha
L
L
Gregorio
A
A
Ferlito
F
F
Rossi
F
F
Jarrossay
D
D
Lanzavecchia
A
A
Martini
A
A
Manz
M G
MG
D000293:Adolescent; D001171:Arthritis, Juvenile / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000096:biosynthesis*; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D013582:Synovial Fluid / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha