title: Temporal changes in salivary glands of non-obese diabetic mice as a model for Sjögren's syndrome.
abstract: OBJECTIVE
  Non-obese diabetic (NOD) mice develop an autoimmune exocrinopathy that shows similarities with Sjögren's syndrome. They provide an experimental model to study the pathoetiogenesis of this disease.
  
  
  METHODS
  Salivary gland (SG) function and salivary sodium content were measured in 8-, 12-, 16- and 20-week-old NOD and age-matched CB6 mice. In NOD mice, SG expression of phenotypic cell markers, B cell-stimulating and costimulatory molecules were evaluated. Cytokine levels were measured in serum and SG homogenates.
  
  
  RESULTS
  Microscopically evident SG inflammation in NOD mice was preceded by expression of intercellular adhesion molecule 1 on epithelial cells in the presence of macrophages and relatively high levels of cytokines. Next, an influx consisting of mainly T, B, natural killer, plasma and dendritic cells was seen. Most cytokines, except for interleukin (IL)12/IL23p40 and B cell-activating factor, decreased or remained stable over time, while glandular function deteriorated from 16 weeks of age onward compared with CB6 mice.
  
  
  CONCLUSIONS
  Sjögren's syndrome-like disease in NOD mice occurs in multiple stages; immunological and physiological abnormalities can be detected before focal inflammation appears and salivary output declines. Extrapolating this knowledge to human subjects could help in understanding the pathogenesis and aid the identification of potential therapeutic targets.
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. n.roescher@amc.uva.nl
authors.forename: N
authors.initials: N
authors.lastname: Roescher
authors.forename: B M
authors.initials: BM
authors.lastname: Lodde
authors.forename: J L
authors.initials: JL
authors.lastname: Vosters
authors.forename: P P
authors.initials: PP
authors.lastname: Tak
authors.forename: M A
authors.initials: MA
authors.lastname: Catalan
authors.forename: G G
authors.initials: GG
authors.lastname: Illei
authors.forename: J A
authors.initials: JA
authors.lastname: Chiorini
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000097:blood; D007378:Interleukins / Q000096:biosynthesis / Q000097:blood; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D012463:Saliva / Q000737:chemistry / Q000378:metabolism; D012469:Salivary Glands / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D012636:Secretory Rate; D012793:Sialadenitis / Q000473:pathology / Q000503:physiopathology*; D012859:Sjogren's Syndrome / Q000209:etiology* / Q000276:immunology*; D012964:Sodium / Q000032:analysis; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors
chemical_list: D053264:B-Cell Activating Factor; D019013:CD40 Antigens; D016207:Cytokines; D007378:Interleukins; C505720:Tnfsf13b protein, mouse; D018799:Intercellular Adhesion Molecule-1; D012964:Sodium