{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:49:03Z","timestamp":1791848943939,"version":"4.3.4"},"reference-count":33,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:p>Sj\u00f6gren\u2019s syndrome (SS) is an inflammatory autoimmune disease that causes secretory dysfunction of the salivary glands. It has been reported that proinflammatory cytokine interleukin-17 (IL-17) was elevated and tight junction (TJ) integrity disrupted in minor salivary glands from SS patients. However, whether the elevated IL-17 in SS affects TJ integrity and thereby alters the function of salivary gland is unknown. Here, by using nonobese diabetic (NOD) mice as SS model, we found that the stimulated salivary flow rate was significantly decreased in NOD mice. Lymphocyte infiltration was mainly observed in submandibular glands (SMGs), but not parotid glands (PGs), of NOD mice. IL-17 was significantly increased and mainly located in lymphocytic-infiltrating regions in SMGs but not detectable in PGs of NOD mice. Meanwhile, the epithelial barrier function was disrupted, as evidenced by an increased paracellular tracer clearance and an enlarged acinar TJ width in SMGs of NOD mice. Furthermore, claudin-1 and -3 were elevated especially at the basolateral membranes, whereas claudin-4, occludin, and zonula occludens\u20131 (ZO-1) were reduced in SMGs of NOD mice. Moreover, occludin and ZO-1 were dispersed into cytoplasm in SMGs of NOD mice. However, no change in the expression and distribution of TJ proteins was found in PGs. In vitro, IL-17 significantly decreased the levels and apical staining of claudin-4 and ZO-1 proteins in the cultured SMG tissues, as well as claudin-1, occludin, and ZO-1 in PG tissues. Moreover, IL-17 activated the phosphorylation of I\u03baB\u03b1 and p65 in SMG cells, whereas pretreatment with NF-\u03baB inhibitor pyrrolidine dithiocarbamate suppressed the IL-17-induced downregulation of claudin-4 and ZO-1 in SMG tissues. Taken together, these findings indicate that IL-17 derived from infiltrating lymphocyte impairs the integrity of TJ barrier through NF-\u03baB signaling pathway, and thus might contribute to salivary gland dysfunction in SS.<\/jats:p>","DOI":"10.1177\/0022034516634647","type":"journal-article","created":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T23:05:35Z","timestamp":1456873535000},"page":"784-792","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":59,"title":["Interleukin-17 Impairs Salivary Tight Junction Integrity in Sj\u00f6gren\u2019s Syndrome"],"prefix":"10.1177","volume":"95","author":[{"given":"L.W.","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Oral Medicine and Center for Salivary Gland Diseases of Peking University School and Hospital of Stomatology, Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.C.","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.C.A.","family":"Serr\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, P.R. China"},{"name":"Department of Dentistry, Santa Cec\u00edlia University, Santos, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"A.R.T.","family":"Brito","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, P.R. China"},{"name":"Department of Dentistry, Santa Cec\u00edlia University, Santos, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.Y.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Center for Salivary Gland Diseases of Peking University School and Hospital of Stomatology, Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.L.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, P.R. 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