title: Loss of PKCδ results in characteristics of Sjögren's syndrome including salivary gland dysfunction.
abstract: OBJECTIVE
  Chronic infiltration of lymphocytes into the salivary and lacrimal glands of patients with Sjögren's syndrome (SS) leads to destruction of acinar cells and loss of exocrine function. Protein kinase C-delta (PKCδ) is known to play a critical role in B-cell maintenance. Mice in which the PKCδ gene has been disrupted have a loss of B-cell tolerance, multiple organ lymphocytic infiltration, and altered apoptosis. To determine whether PKCδ contributes to the pathogenesis of SS, we quantified changes in indicators of SS in PKCδ-/- mice as a function of age. Salivary gland histology, function, the presence of autoantibodies, and cytokine expression were examined.
  
  
  METHODS
  Submandibular glands were examined for the presence of lymphocytic infiltrates, and the type of infiltrating lymphocyte and cytokine deposition was evaluated by immunohistochemistry. Serum samples were tested by autoantibody screening, which was graded by its staining pattern and intensity. Salivary gland function was determined by saliva collection at various ages.
  
  
  RESULTS
  PKCδ-/- mice have reduced salivary gland function, B220+ B-cell infiltration, anti-nuclear antibody production, and elevated IFN-γ in the salivary glands as compared to PKCδ+/+ littermates.
  
  
  CONCLUSIONS
  PKCδ-/- mice have exocrine gland tissue damage indicative of a SS-like phenotype.
authors.affiliation: Department of Craniofacial Biology, School of Dental Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: G P
authors.initials: GP
authors.lastname: Banninger
authors.forename: S
authors.initials: S
authors.lastname: Cha
authors.forename: M S
authors.initials: MS
authors.lastname: Said
authors.forename: K M
authors.initials: KM
authors.lastname: Pauley
authors.forename: C J
authors.initials: CJ
authors.lastname: Carter
authors.forename: M
authors.initials: M
authors.lastname: Onate
authors.forename: B A
authors.initials: BA
authors.lastname: Pauley
authors.forename: S M
authors.initials: SM
authors.lastname: Anderson
authors.forename: M E
authors.initials: ME
authors.lastname: Reyland
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D017209:Apoptosis / Q000235:genetics; D001323:Autoantibodies / Q000032:analysis / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D018858:Germinal Center / Q000473:pathology; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D051745:Protein Kinase C-delta / Q000235:genetics / Q000276:immunology*; D018987:Salivary Ducts / Q000276:immunology / Q000473:pathology; D012636:Secretory Rate / Q000502:physiology; D017634:Self Tolerance / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology*; D013363:Submandibular Gland / Q000378:metabolism / Q000473:pathology; D013364:Submandibular Gland Diseases / Q000276:immunology* / Q000503:physiopathology
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D019394:Ki-67 Antigen; D015847:Interleukin-4; D007371:Interferon-gamma; D051745:Protein Kinase C-delta; D017493:Leukocyte Common Antigens