Distinct expression pattern of IFN- (cid:1) and TNF- (cid:1) in juvenile idiopathic arthritis synovial tissue

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)- (cid:1) and tumour necrosis factor (TNF)- (cid:1) , respectively. We here investigated the presence and characteristics of natural type I IFN-producing cells (IPCs), as well as IFN- (cid:1) and TNF- (cid:1) expression at sites of inflammation in juvenile idiopathic arthritis (JIA). Methods . Peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MNCs) ( n ¼ 25 each) from JIA patients with active disease were studied. IPCs were identified as BCDA-2 þ CD123 þ HLA-DR þ CD45RA þ cells, and dendritic cells (DCs) as CD11c þ CD14 (cid:1) /low lin (cid:1) 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- (cid:1) was measured by enzyme-linked immunosorbent assay in serum, SF and in supernatants of influenza virus-infected, cultured IPCs. Synovial tissues of n ¼ 6 additional JIA patients were analysed by immunohistochemistry using mAbs against CD123, IFN- (cid:1) , TNF- (cid:1) , 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- (cid:1) release was detected from SF IPCs, and serum and SF IFN- (cid:1) levels were not elevated. Nonetheless, in synovial tissue IFN- (cid:1) producing cells accumulated at inflammatory lymph-follicular-like structures, while TNF- (cid:1) producing cells were mostly found at the lining and sublining layers. Conclusions . These data suggest that besides TNF- (cid:1) -expressing cells, IFN- (cid:1) -producing IPCs are involved in initiation, maintenance or regulation of the inflammatory response in JIA.

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