| Abstract | OBJECTIVES: 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. |
| Authors | M Gattorno, L Chicha, A Gregorio, F Ferlito, F Rossi, D Jarrossay, A Lanzavecchia, A Martini, M G Manz
(Affiliation: Second Division of Pediatrics, G. Gaslini Institute and University of Genoa, Largo G. Gaslini 5, 16147, Genoa, Italy. marcogattorno at ospedale-gaslini.ge.it)
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| Journal | Rheumatology (Oxford, England)
(Rheumatology (Oxford))
Vol. 46
Issue 4
Pg. 657-65
(Apr 2007)
ISSN: 1462-0324 England |
| PMID | 17085467
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Interferon-alpha
- Tumor Necrosis Factor-alpha
|
| Topics |
- Adolescent
- Arthritis, Juvenile Rheumatoid
(immunology)
- Autoimmune Diseases
(immunology)
- Child
- Child, Preschool
- Dendritic Cells
(immunology)
- Female
- Humans
- Immunoenzyme Techniques
- Immunophenotyping
- Interferon-alpha
(biosynthesis)
- Male
- Polymerase Chain Reaction
(methods)
- Synovial Fluid
(immunology)
- Synovial Membrane
(immunology)
- Tumor Necrosis Factor-alpha
(biosynthesis)
|
