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IL-4-STAT6 signal transduction-dependent induction of the clinical phase of Sjögren's syndrome-like disease of the nonobese diabetic mouse.

Publication ,  Journal Article
Nguyen, CQ; Gao, J-H; Kim, H; Saban, DR; Cornelius, JG; Peck, AB
Published in: J Immunol
July 1, 2007

NOD.B10-H2(b) and NOD/LtJ mice manifest, respectively, many features of primary and secondary Sjögren's syndrome (SjS), an autoimmune disease affecting primarily the salivary and lacrimal glands leading to xerostomia (dry mouth) and xerophthalmia (dry eyes). B lymphocytes play a central role in the onset of SjS with clinical manifestations dependent on the appearance of autoantibodies reactive to multiple components of acinar cells. Previous studies with NOD.IL4(-/-) and NOD.B10-H2(b).IL4(-/-) mice suggest that the Th2 cytokine, IL-4, plays a vital role in the development and onset of SjS-like disease in the NOD mouse model. To investigate the molecular mechanisms by which IL-4 controls SjS development, a Stat6 gene knockout mouse, NOD.B10-H2(b).C-Stat6(-/-), was constructed and its disease profile was defined and compared with that of NOD.B10-H2(b).C-Stat6(+/+) mice. As the NOD.B10-H2(b).C-Stat6(-/-) mice aged from 4 to 24 wk, they exhibited leukocyte infiltration of the exocrine glands, produced anti-nuclear autoantibodies, and showed loss and gain of saliva-associated proteolytic enzymes, similar to NOD.B10-H2(b).C-Stat6(+/+) mice. In contrast, NOD.B10-H2(b).C-Stat6(-/-) mice failed to develop glandular dysfunction, maintaining normal saliva flow rates. NOD.B10-H2(b).C-Stat6(-/-) mice were found to lack IgG1 isotype-specific anti-muscarinic acetylcholine type-3 receptor autoantibodies. Furthermore, the IgG fractions from NOD.B10-H2(b).C-Stat6(-/-) sera were unable to induce glandular dysfunction when injected into naive recipient C57BL/6 mice. NOD.B10-H2(b).C-Stat6(-/-) mice, like NOD.B10-H2(b).IL4(-/-) mice, are unable to synthesize IgG1 Abs, an observation that correlates with an inability to develop end-stage clinical SjS-like disease. These data imply a requirement for the IL-4/STAT6-pathway for onset of the clinical phase of SjS-like disease in the NOD mouse model.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

July 1, 2007

Volume

179

Issue

1

Start / End Page

382 / 390

Location

United States

Related Subject Headings

  • Sjogren's Syndrome
  • Signal Transduction
  • STAT6 Transcription Factor
  • Receptor, Muscarinic M3
  • Phenotype
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred NOD
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
 

Citation

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MLA
NLM
Nguyen, C. Q., Gao, J.-H., Kim, H., Saban, D. R., Cornelius, J. G., & Peck, A. B. (2007). IL-4-STAT6 signal transduction-dependent induction of the clinical phase of Sjögren's syndrome-like disease of the nonobese diabetic mouse. J Immunol, 179(1), 382–390. https://doi.org/10.4049/jimmunol.179.1.382
Nguyen, Cuong Q., Jue-hua Gao, Hyuna Kim, Daniel R. Saban, Janet G. Cornelius, and Ammon B. Peck. “IL-4-STAT6 signal transduction-dependent induction of the clinical phase of Sjögren's syndrome-like disease of the nonobese diabetic mouse.J Immunol 179, no. 1 (July 1, 2007): 382–90. https://doi.org/10.4049/jimmunol.179.1.382.
Nguyen CQ, Gao J-H, Kim H, Saban DR, Cornelius JG, Peck AB. IL-4-STAT6 signal transduction-dependent induction of the clinical phase of Sjögren's syndrome-like disease of the nonobese diabetic mouse. J Immunol. 2007 Jul 1;179(1):382–90.
Nguyen, Cuong Q., et al. “IL-4-STAT6 signal transduction-dependent induction of the clinical phase of Sjögren's syndrome-like disease of the nonobese diabetic mouse.J Immunol, vol. 179, no. 1, July 2007, pp. 382–90. Pubmed, doi:10.4049/jimmunol.179.1.382.
Nguyen CQ, Gao J-H, Kim H, Saban DR, Cornelius JG, Peck AB. IL-4-STAT6 signal transduction-dependent induction of the clinical phase of Sjögren's syndrome-like disease of the nonobese diabetic mouse. J Immunol. 2007 Jul 1;179(1):382–390.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

July 1, 2007

Volume

179

Issue

1

Start / End Page

382 / 390

Location

United States

Related Subject Headings

  • Sjogren's Syndrome
  • Signal Transduction
  • STAT6 Transcription Factor
  • Receptor, Muscarinic M3
  • Phenotype
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred NOD
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C