期刊
CURRENT PHARMACEUTICAL BIOTECHNOLOGY
卷 13, 期 10, 页码 2054-2062出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138920112802273290
关键词
Immune complexes; interferon-alpha; IRF5; minor salivary glands; plasmacytoid dendritic cells; primary Sjogren's syndrome; SSA/SSB; STAT4; type I interferon
资金
- Swedish Research Council
- Dana Foundation
- Swedish Rheumatism Association
- King Gustaf V 80 Birthday Foundation
- Torsten and Ragnar Soderberg Foundation
- COMBINE
Patients with primary Sjogren's syndrome (pSS) have an activated type I interferon (IFN) system that contribute to the etiopathogenesis and clinical manifestations of the disease. The type I IFN system consists of the stimuli for type I IFN production, the receptors, cells and transcription factors involved in the synthesis of type I IFNs, the type I IFN-receptor and the effects on target cells. Increased type I IFN activity has been demonstrated in sera from patients with pSS and IFN-alpha, the main type I IFN, has been detected in the minor salivary glands. Gene expression profiling of peripheral blood mononuclear cells (PBMCs) and minor salivary glands from pSS patients display an up-regulation of type I IFN-induced genes, an IFN signature. The professional IFN-alpha producing plasmacytoid dendritic cell (pDC) shows a reduced frequency in the peripheral blood, but has been detected in the salivary glands, possibly due to tissue recruitment. Polymorphisms in the interferon regulatory factor 5 (IRF5) and signal transducer and activator of transcription 4 (STAT4) genes in the type I IFN system, are associated with increased risk for pSS. A postulated disease model is that an initial viral infection induces type I IFN production in the salivary glands with subsequent activation of the adaptive immune system resulting in the production of autoantibodies against the RNA-binding proteins SSA/SSB/RNP. Interferogenic immune complexes are formed, which trigger the pDCs to an ongoing type I IFN production, which sustain the disease process. Potential therapeutic targets can be identified within the type I IFN system.
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