title: Pathogenic effect of interleukin-17A in induction of Sjögren's syndrome-like disease using adenovirus-mediated gene transfer.
abstract: BACKGROUND
  Sjögren's syndrome (SS) involves a chronic, progressive inflammation primarily of the salivary and lacrimal glands leading to decreased levels of saliva and tears resulting in dry mouth and dry eye diseases. Seminal findings regarding TH17 cell populations that secrete predominantly interleukin (IL)-17A have been shown to play an important role in an increasing number of autoimmune diseases, including SS. In the present study, we investigated the function of IL-17A on the development and onset of SS.
  
  
  METHODS
  Adenovirus serotype 5 (Ad5) vectors expressing either IL-17A or LacZ were infused via retrograde cannulation into the salivary glands of C57BL/6J mice between 6 and 8 weeks of age or between 15 and 17 weeks of age. The mice were characterized for SS phenotypes.
  
  
  RESULTS
  Disease profiling indicated that SS-non-susceptible C57BL/6J mice whose salivary glands received the Ad5-IL17A vector developed a SS-like disease profile, including the appearance of lymphocytic foci, increased cytokine levels, changes in antinuclear antibody profiles, and temporal loss of saliva flow.
  
  
  CONCLUSIONS
  Induction of SS pathology by IL-17A in SS-non-susceptible mice strongly suggests that IL-17A is an important inflammatory cytokine in salivary gland dysfunction. Thus, localized anti-IL17 therapy may be effective in preventing glandular dysfunction.
authors.affiliation: Eli and Edythe L, Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA. Nguyen@pathology.ufl.edu
authors.forename: Cuong Q
authors.initials: CQ
authors.lastname: Nguyen
authors.forename: Hongen
authors.initials: H
authors.lastname: Yin
authors.forename: Byung Ha
authors.initials: BH
authors.lastname: Lee
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Carcamo
authors.forename: John A
authors.initials: JA
authors.lastname: Chiorini
authors.forename: Ammon B
authors.initials: AB
authors.lastname: Peck
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D002469:Cell Separation; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012469:Salivary Glands / Q000276:immunology* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology*; D014161:Transduction, Genetic
chemical_list: D000974:Antibodies, Antinuclear; D020381:Interleukin-17; D015850:Interleukin-6