Temporal changes in salivary glands of non-obese diabetic mice as a model for Sjögren's syndrome

Oral Dis. 2012 Jan;18(1):96-106. doi: 10.1111/j.1601-0825.2011.01852.x. Epub 2011 Sep 14.

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.

Materials and 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Cell Activating Factor / biosynthesis
  • CD40 Antigens / biosynthesis
  • Cytokines / biosynthesis
  • Cytokines / blood
  • Disease Models, Animal*
  • Female
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Intercellular Adhesion Molecule-1 / blood
  • Interleukins / biosynthesis
  • Interleukins / blood
  • Lymphocytes / immunology
  • Macrophages / immunology
  • Mice
  • Mice, Inbred NOD
  • Mice, Inbred Strains
  • Saliva / chemistry
  • Saliva / metabolism
  • Salivary Glands / chemistry
  • Salivary Glands / pathology
  • Salivary Glands / physiopathology*
  • Secretory Rate
  • Sialadenitis / pathology
  • Sialadenitis / physiopathology*
  • Sjogren's Syndrome / etiology*
  • Sjogren's Syndrome / immunology*
  • Sodium / analysis
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Time Factors

Substances

  • B-Cell Activating Factor
  • CD40 Antigens
  • Cytokines
  • Interleukins
  • Tnfsf13b protein, mouse
  • Intercellular Adhesion Molecule-1
  • Sodium