Sjögren's syndrome in the NOD mouse model is an interleukin-4 time-dependent, antibody isotype-specific autoimmune disease

Juehua Gao, Smruti Killedar, Janet G. Cornelius, Cuong Nguyen, Seunghee Cha, Ammon B. Peck*

*Corresponding author for this work

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

NOD.B10-H2b and NOD/LtJ mice manifest many features of primary and secondary Sjögren's syndrome (SjS), respectively, an autoimmune disease affecting primarily the salivary and lacrimal glands leading to xerostomia (dry mouth) and xerophthalmia (dry eyes). A previous study suggested that the T H2 cytokine, interleukin (IL)-4, plays an integral role in the development and onset of SjS-like disease in the NOD mouse model. To define further the role of IL-4 in onset of murine SjS-like disease, we have examined two IL4 gene knockout (KO) mouse strains, NOD.IL4-/- and NOD.B10-H2b.IL4-/-. Unlike NOD.IL4-/- mice, NOD.B10-H2b.IL4-/- mice are resistant to development of diabetes. The presence of a dysfunctional IL4 gene did not impede leukocyte infiltration of the salivary glands, yet prevented development of secretory dysfunction. Whereas NOD.B10-H2b.IL4-/- mice exhibited many pathophysiological manifestations of SjS-like disease common to the parental strains, these mice failed to produce anti-muscarinic acetylcholine type-3 receptor (M3R) autoantibodies of the IgG1 isotype. Cytokine mRNA expression profiles and adoptive transfers of T lymphocytes from NOD.B10-H2 b.Gfp mice into NOD.B10-H2b.IL4-/- mice at different ages suggest IL-4 is required during the pre-clinical disease stage (around 12 weeks of age) to initiate clinical xerostomia. The results of this study indicate that the failure of NOD.IL4-/- and NOD.B10-H2 b.IL4-/- mice to synthesize anti-M3R autoantibodies of the IgG1 isotype apparently explains why these mice fail to develop exocrine gland dysfunction, despite exhibiting pre-clinical manifestations of SjS-like disease.

Original languageEnglish (US)
Pages (from-to)90-103
Number of pages14
JournalJournal of Autoimmunity
Volume26
Issue number2
DOIs
StatePublished - Mar 1 2006

Keywords

  • Anti-muscarinic acetylcholine type-3 receptor autoantibodies
  • Interleukin-4
  • NOD mouse
  • Sjögren's syndrome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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