A dual role for interferon-γ in the pathogenesis of Sjögren's syndrome-like autoimmune exocrinopathy in the nonobese diabetic mouse

S. Cha, J. Brayer, J. Gao, V. Brown, S. Killedar, U. Yasunari, A. B. Peck*

*Corresponding author for this work

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Sjögren's syndrome-like autoimmune exocrinopathy (AEC) in the nonobese diabetic (NOD) mouse progresses from a preimmune phase to an immune phase, resulting in dry mouth and/or dry eyes. In the present study, the impact of the prototypical T-helper type 1 cytokine, interferon-gamma (IFN-γ), on the onset of AEC was investigated using both the IFN-γ and the IFN-γ receptor gene knockout mice, NOD.IFN-γR-/- and NOD.IFN-γR-/-, respectively. Neither the NOD.IFN-γ -/- nor the NOD.IFN-γR-/- mice exhibited increased acinar cell apoptosis and abnormal salivary protein expression, typically observed in parental NOD mice prior to disease. Without these preimmune phase abnormalities, NOD.IFN-γ-/- and NOD.IFN-γR-/- mice showed no subsequent autoimmune responses against the salivary glands at 20 weeks. Interestingly, real-time polymerase chain reaction and electrophoretic gel mobility shift assays suggested that IFN-γ and STAT1, as well as the transcriptional activity of STAT1 in NOD glands, were increased at birth. Unlike the neonatal submandibular glands of NOD or NOD-scid mice that show abnormal glandular morphogenesis at birth, the submandibular glands of the newly constructed congenic strain, NOD-scid.IFN-γ-/-, were found to be normal. Taken together, IFN-γ appears to play a critical role not only during the later immune phase of AEC, but also the early preimmune phase, independent of effector functions of immune cells. How exactly IFN-γ functions during this period remains speculative.

Original languageEnglish (US)
Pages (from-to)552-565
Number of pages14
JournalScandinavian Journal of Immunology
Volume60
Issue number6
DOIs
StatePublished - Dec 1 2004

ASJC Scopus subject areas

  • Immunology

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