{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:32:32Z","timestamp":1791322352789,"version":"4.3.1"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,7,26]],"date-time":"2013-07-26T00:00:00Z","timestamp":1374796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["P30-DE-020751"],"award-info":[{"award-number":["P30-DE-020751"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Although elevated interleukin\u20107 (IL\u20107) levels have been reported in patients with primary Sj\u00f6gren's syndrome (SS), the role of IL\u20107 in this disease remains unclear. We undertook this study to characterize the previously unexplored role of IL\u20107 in the development and onset of primary SS using the C57BL\/6.NOD\u2010<jats:italic>Aec1Aec2<\/jats:italic> (B6.NOD\u2010<jats:italic>Aec<\/jats:italic>) mouse model, which recapitulates human primary SS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>For gain\u2010of\u2010function studies, recombinant IL\u20107 or control phosphate buffered saline was injected intraperitoneally (IP) into 12\u2010week\u2010old B6.NOD\u2010<jats:italic>Aec<\/jats:italic> mice for 8 weeks. For loss\u2010of\u2010function studies, anti\u2013IL\u20107 receptor \u03b1\u2010chain (anti\u2013IL\u20107R\u03b1) antibody or its isotype control IgG was administered IP into 16\u2010week\u2010old B6.NOD\u2010<jats:italic>Aec<\/jats:italic> mice. Salivary flow measurement, histologic and flow cytometric analysis of salivary glands, and serum antinuclear antibody assay were performed to assess various disease parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Administration of exogenous IL\u20107 accelerated the development of primary SS, whereas blockade of IL\u20107R\u03b1 signaling almost completely abolished the development of primary SS, based on salivary gland inflammation and apoptosis, autoantibody production, and secretory dysfunction. IL\u20107 positively regulated interferon\u2010\u03b3 (IFN\u03b3)\u2013producing Th1 and CD8+ T cells in the salivary glands without affecting IL\u201017. Moreover, IL\u20107 enhanced the expression of CXCR3 ligands in a T cell\u2013 and IFN\u03b3\u2010dependent manner. Accordingly, IFN\u03b3 induced a human salivary gland epithelial cell line to produce CXCR3 ligands. IL\u20107 also increased the level of tumor necrosis factor \u03b1, another Th1\u2010associated cytokine that can facilitate tissue destruction and inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IL\u20107 plays a pivotal pathogenic role in SS, which is underpinned by an enhanced Th1 response and IFN\u03b3\/CXCR3 ligand\u2013mediated lymphocyte infiltration of target organs. These results suggest that targeting the IL\u20107 pathway may be a potential future strategy for preventing and treating SS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38007","type":"journal-article","created":{"date-parts":[[2013,5,10]],"date-time":"2013-05-10T20:10:24Z","timestamp":1368216624000},"page":"2132-2142","source":"Crossref","is-referenced-by-count":65,"title":["Interleukin\u20107 Enhances the Th1 Response to Promote the Development of Sj\u00f6gren's Syndrome\u2013like Autoimmune Exocrinopathy in Mice"],"prefix":"10.1002","volume":"65","author":[{"given":"Jun\u2010O","family":"Jin","sequence":"first","affiliation":[{"name":"The Forsyth Institute Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihisa","family":"Kawai","sequence":"additional","affiliation":[{"name":"The Forsyth Institute Cambridge 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