Interleukin-12 induces salivary gland dysfunction in transgenic mice, providing a new model of Sjögren's syndrome.

Jelle L Vosters, Melissa A Landek-Salgado, Hongen Yin, William D Swaim, Hiroaki Kimura, Paul P Tak, Patrizio Caturegli, John A Chiorini
Author Information
  1. Jelle L Vosters: National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, USA.

Abstract

OBJECTIVE: Interleukin-12 (IL-12) is a pleiotropic cytokine that is elevated in the affected organs of patients with Sjögren's syndrome (SS). We have previously reported that overexpression of IL-12 in CBA mice leads to mononuclear infiltration of salivary and lacrimal glands, as well as to expansion of bronchial lymphoid tissue and decreased mucociliary clearance. Because xerostomia is one of the most important clinical features in SS patients, our main objective in the current study was to evaluate salivary gland function in IL-12-transgenic mice. Our secondary objective was to further characterize this animal model and to determine if the changes observed in these mice are representative of those observed in patients with SS overall.
METHODS: Pilocarpine-stimulated salivary flow was used to address salivary gland function in a large group of IL-12-transgenic mice bred onto the autoimmune-prone SJL background. Furthermore, salivary glands were removed to assess the formation of infiltrates in the glands and gland morphology. Serum was also collected from these animals to investigate the formation of autoantibodies.
RESULTS: Pilocarpine-stimulated salivary flow was significantly lower in IL-12-transgenic mice than in wild-type controls. Salivary glands from transgenic mice exhibited an increase in both the number and the size of lymphocytic foci, versus glands from age-matched controls. Furthermore, the acini in transgenic mice were fewer in number and larger in size compared with acini in controls. An age-dependent increase in anti-SSB/La antibodies was observed in IL-12-transgenic mice and was accompanied by an increase in antinuclear antibodies.
CONCLUSION: Our findings indicate that a number of conditions associated with SS are exhibited by IL-12-transgenic SJL mice and that this model might be useful in researching multiple aspects of the disease.

References

Clin Exp Immunol. 2007 Mar;147(3):513-20 [PMID: 17302901]
Oral Dis. 2006 Nov;12(6):566-72 [PMID: 17054769]
Cell Mol Life Sci. 1999 Sep;55(12):1610-25 [PMID: 10526578]
Clin Immunol. 1999 Sep;92(3):265-75 [PMID: 10479531]
J Immunol. 1983 Jan;130(1):203-8 [PMID: 6600176]
Am J Physiol Lung Cell Mol Physiol. 2006 Oct;291(4):L837-46 [PMID: 16751222]
Blood. 1994 Dec 15;84(12):4008-27 [PMID: 7994020]
Am J Physiol. 1992 Oct;263(4 Pt 1):E607-14 [PMID: 1415679]
J Clin Invest. 2006 Dec;116(12):3183-94 [PMID: 17143328]
Immunol Today. 1995 Aug;16(8):383-6 [PMID: 7546194]
Hum Gene Ther. 2003 Nov 20;14(17):1605-18 [PMID: 14633403]
Clin Immunol Immunopathol. 1993 Sep;68(3):350-6 [PMID: 8370186]
Proc Natl Acad Sci U S A. 1995 May 23;92(11):4823-7 [PMID: 7761407]
J Rheumatol. 2002 May;29(5):938-44 [PMID: 12022353]
Clin Immunol. 2002 May;103(2):111-24 [PMID: 12027416]
Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3621-6 [PMID: 17360692]
Clin Rheumatol. 2007 Oct;26(10):1601-6 [PMID: 17558463]
Ann Rheum Dis. 2000 Sep;59(9):709-12 [PMID: 10976085]
Endocrinology. 2005 Aug;146(8):3642-51 [PMID: 15860554]
J Exp Med. 1996 Apr 1;183(4):1447-59 [PMID: 8666903]
Scand J Rheumatol. 1995;24(5):300-4 [PMID: 8533045]
Ann Rheum Dis. 2006 Feb;65(2):195-200 [PMID: 15975969]
Cytokine. 2000 Jul;12(7):1035-41 [PMID: 10880249]

Grants

  1. ZIA DE000695/Intramural NIH HHS

MeSH Term

Animals
Antibodies, Antinuclear
Biomarkers
Body Weight
Cell Enlargement
Cell Proliferation
Cholinergic Agents
Disease Models, Animal
Female
Interleukin-12
Lacrimal Apparatus
Leukocytes, Mononuclear
Male
Mice
Mice, Transgenic
Pilocarpine
Salivary Glands
Sex Factors
Sjogren's Syndrome

Chemicals

Antibodies, Antinuclear
Biomarkers
Cholinergic Agents
Pilocarpine
Interleukin-12