Primary Sjögren's syndrome and the type I interferon system.
Patients with primary Sjögren'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-α, 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-α 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.
Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden. Gunnel.Nordmark@medsci.uu.se
Gunnel
G
Nordmark
Maija-Leena
ML
Eloranta
Lars
L
Ronnblom
D001323:Autoantibodies / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000097:blood / Q000235:genetics / Q000276:immunology; D012470:Salivary Glands, Minor / Q000276:immunology / Q000473:pathology; D012859:Sjogren's Syndrome / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D001323:Autoantibodies; D007370:Interferon Type I