1. Distinct expression pattern of IFN- and TNF- in juvenile idiopathic arthritis synovial tissue
- Author
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Andrea Gregorio, L. Chicha, A. Lanzavecchia, Alberto Martini, D. Jarrossay, Francesca Ferlito, Marco Gattorno, F. Rossi, and M. G. Manz
- Subjects
Male ,Adolescent ,Plasmacytoid cells ,medicine.medical_treatment ,Juvenile ,Arthritis ,Polymerase Chain Reaction ,Autoimmune Diseases ,Immunophenotyping ,Immunoenzyme Techniques ,Rheumatology ,Synovial Fluid ,medicine ,Humans ,Synovial fluid ,Pharmacology (medical) ,Preschool ,Child ,skin and connective tissue diseases ,Tumor Necrosis Factor-alpha ,business.industry ,Synovial Membrane ,Interferon-alpha ,Dendritic Cells ,Dendritic cell ,Juvenile idiopathic arthritis ,medicine.disease ,Arthritis, Juvenile ,Dendritic cells ,Interferon-α ,Child, Preschool ,Female ,Cytokine ,medicine.anatomical_structure ,Rheumatoid arthritis ,Immunology ,Tumor necrosis factor alpha ,Synovial membrane ,business ,Juvenile rheumatoid arthritis - Abstract
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).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.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.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.
- Published
- 2006