{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:34:14Z","timestamp":1792056854431,"version":"4.4.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2007,7,1]],"date-time":"2007-07-01T00:00:00Z","timestamp":1183248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>NOD.B10-H2b and NOD\/LtJ mice manifest, respectively, many features of primary and secondary Sjo\u0308gren\u2019s 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\u2212\/\u2212 and NOD.B10-H2b.IL4\u2212\/\u2212 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-H2b.C-Stat6\u2212\/\u2212, was constructed and its disease profile was defined and compared with that of NOD.B10-H2b.C-Stat6+\/+ mice. As the NOD.B10-H2b.C-Stat6\u2212\/\u2212 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-H2b.C-Stat6+\/+ mice. In contrast, NOD.B10-H2b.C-Stat6\u2212\/\u2212 mice failed to develop glandular dysfunction, maintaining normal saliva flow rates. NOD.B10-H2b.C-Stat6\u2212\/\u2212 mice were found to lack IgG1 isotype-specific anti-muscarinic acetylcholine type-3 receptor autoantibodies. Furthermore, the IgG fractions from NOD.B10-H2b.C-Stat6\u2212\/\u2212 sera were unable to induce glandular dysfunction when injected into naive recipient C57BL\/6 mice. NOD.B10-H2b.C-Stat6\u2212\/\u2212 mice, like NOD.B10-H2b.IL4\u2212\/\u2212 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.<\/jats:p>","DOI":"10.4049\/jimmunol.179.1.382","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:38:23Z","timestamp":1397864303000},"page":"382-390","source":"Crossref","is-referenced-by-count":53,"title":["IL-4-STAT6 Signal Transduction-Dependent Induction of the Clinical Phase of Sjo\u0308gren\u2019s Syndrome-Like Disease of the Nonobese Diabetic Mouse"],"prefix":"10.1093","volume":"179","author":[{"given":"Cuong Q","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue-hua","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyuna","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R","family":"Saban","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet G","family":"Cornelius","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammon B","family":"Peck","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida , Gainesville, FL 32610"},{"name":"Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FL 32610"},{"name":"Center for Orphan Autoimmune Diseases, College of Dentistry, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,7,1]]},"reference":[{"key":"2025032701450779100_R1","first-page":"517","volume-title":"Rheum. 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