title: Aspects of innate immunity in Sjögren's syndrome.
abstract: Previously, a dominant role of the adaptive immune system in the pathogenesis of Sjögren's syndrome was suspected. Recent advances, however, have revealed a major role of the type I IFN pathway, documented by an increased circulating type I IFN activity and an IFN 'signature' in peripheral blood mononuclear cells and minor salivary gland biopsies from the patients. Polymorphisms in the genes IRF5 and STAT4 leading to increased IFN activation are associated with disease susceptibility. In the pathogenesis of Sjögren's syndrome, the activation of salivary gland epithelial cells appears to be the initial event. Once intrinsically activated, they express costimulatory and Toll-like receptors (TLRs) and MHC class I and II molecules, can present autoantigens and produce proinflammatory cytokines. The subsequent activation of plasmacytoid dendritic cells induces the production of high levels of proinflammatory cytokines in individuals with the risk alleles of the susceptibility genes IRF5 and STAT4. Under the influence of the high IFN concentration in the glands and through TLR ligation, B-cell activating factor is produced by epithelial cells and, together with autoantigen presentation on salivary gland epithelial cells, stimulates the adaptive immune system. In view of the central role of IFNalpha in at least the initiation of the pathogenesis of Sjögren's syndrome, blockade of this cytokine may be a rational therapeutic approach.
authors.affiliation: Clinic for Immunology and Rheumatology, Medical School Hannover, Carl-Neuberg-Str, 1, 30625 Hannover, Germany.
authors.forename: Hui Zhi
authors.initials: HZ
authors.lastname: Low
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
mesh_terms: D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D012469:Salivary Glands / Q000276:immunology*; D015398:Signal Transduction; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology*