Distinct expression pattern of IFN-α and TNF-α in juvenile idiopathic arthritis synovial tissue

Marco Gattorno, L. Chicha, A. Gregorio, F. Ferlito, F. Rossi, D. Jarrossay, A. Lanzavecchia, A. Martini, M. G. Manz

Research output: Contribution to journalArticlepeer-review

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)-α and tumour necrosis factor (TNF)-α, respectively. We here investigated the presence and characteristics of natural type I IFN-producing cells (IPCs), as well as IFN-α and TNF-α 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 -/lowlin - 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-α 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-α, TNF-α, 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-α release was detected from SF IPCs, and serum and SF IFN-α levels were not elevated. Nonetheless, in synovial tissue IFN-α producing cells accumulated at inflammatory lymph-follicular-like structures, while TNF-α producing cells were mostly found at the lining and sublining layers. Conclusions. These data suggest that besides TNF-α-expressing cells, IFN-α-producing IPCs are involved in initiation, maintenance or regulation of the inflammatory response in JIA.

Original languageEnglish
Pages (from-to)657-665
Number of pages9
JournalRheumatology
Volume46
Issue number4
DOIs
Publication statusPublished - Apr 2007

Keywords

  • Dendritic cells
  • Interferon-α
  • Juvenile idiopathic arthritis
  • Plasmacytoid cells

ASJC Scopus subject areas

  • Neuroscience(all)
  • Rheumatology

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