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- Title
A Dual Role for Interferon-γ in the Pathogenesis of Sjögren's Syndrome-Like Autoimmune Exocrinopathy in the Nonobese Diabetic Mouse.
- Authors
Cha, S.; Brayer, J.; Gao, J.; Brown, V.; Killedar, S.; Yasunari, U.; Peck, A. B.
- 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-γ –/– 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-scidmice 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.
- Subjects
INTERFERONS; AUTOIMMUNE diseases; LYMPHOKINES; ANTINEOPLASTIC agents; ANTIVIRAL agents; IMMUNOLOGIC diseases; AUTOIMMUNITY
- Publication
Scandinavian Journal of Immunology, 2004, Vol 60, Issue 6, p552
- ISSN
0300-9475
- Publication type
Article
- DOI
10.1111/j.0300-9475.2004.01508.x