title: Distinct expression pattern of IFN-alpha and TNF-alpha in juvenile idiopathic arthritis synovial tissue.
abstract: 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.
authors.affiliation: Second Division of Pediatrics, G. Gaslini Institute and University of Genoa, Largo G. Gaslini 5, 16147, Genoa, Italy. marcogattorno@ospedale-gaslini.ge.it
authors.forename: M
authors.initials: M
authors.lastname: Gattorno
authors.forename: L
authors.initials: L
authors.lastname: Chicha
authors.forename: A
authors.initials: A
authors.lastname: Gregorio
authors.forename: F
authors.initials: F
authors.lastname: Ferlito
authors.forename: F
authors.initials: F
authors.lastname: Rossi
authors.forename: D
authors.initials: D
authors.lastname: Jarrossay
authors.forename: A
authors.initials: A
authors.lastname: Lanzavecchia
authors.forename: A
authors.initials: A
authors.lastname: Martini
authors.forename: M G
authors.initials: MG
authors.lastname: Manz
mesh_terms: 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*
chemical_list: D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha