{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:51:31Z","timestamp":1777895491723,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIAID","award":["R03 AI142273"],"award-info":[{"award-number":["R03 AI142273"]}]},{"name":"NIH\/NIAID","award":["R01 DE023838"],"award-info":[{"award-number":["R01 DE023838"]}]},{"name":"NIH\/NIAID","award":["R56 DE023838"],"award-info":[{"award-number":["R56 DE023838"]}]},{"name":"NIH\/NIAID","award":["R03 DE028033"],"award-info":[{"award-number":["R03 DE028033"]}]},{"name":"NIH\/NIAID","award":["R01 DE030646"],"award-info":[{"award-number":["R01 DE030646"]}]},{"name":"NIH\/NIDCR","award":["R03 AI142273"],"award-info":[{"award-number":["R03 AI142273"]}]},{"name":"NIH\/NIDCR","award":["R01 DE023838"],"award-info":[{"award-number":["R01 DE023838"]}]},{"name":"NIH\/NIDCR","award":["R56 DE023838"],"award-info":[{"award-number":["R56 DE023838"]}]},{"name":"NIH\/NIDCR","award":["R03 DE028033"],"award-info":[{"award-number":["R03 DE028033"]}]},{"name":"NIH\/NIDCR","award":["R01 DE030646"],"award-info":[{"award-number":["R01 DE030646"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Interleukin-22 (IL-22) affects epithelial tissue function and integrity in a context-dependent manner. IL-22 levels are elevated in salivary glands of Sj\u00f6gren\u2019s syndrome (SS) patients, but its role in the pathogenesis of this disease remains unclear. The objective of this study is to elucidate the impact of IL-22 on salivary gland tissue integrity and function in murine models. We showed that IL-22 levels in sera and salivary glands increased progressively in female non-obese diabetic (NOD) mice, accompanying the development of SS. Administration of IL-22 to the submandibular glands of NOD mice prior to the disease onset reduced salivary secretion and induced caspase-3 activation in salivary gland tissues, which were accompanied by alterations in multiple genes controlling tissue integrity and inflammation. Similarly, IL-22 administration to submandibular glands of C57BL\/6 mice also induced hyposalivation and caspase-3 activation, whereas blockade of endogenous IL-22 in C57BL\/6 mice treated with anti-CD3 antibody mitigated hyposalivation and caspase-3 activation. Finally, IL-22 treatment reduced the number of viable C57BL\/6 mouse submandibular gland epithelial cells cultured in vitro, indicating a direct impact of this cytokine on these cells. We conclude that IL-22 exerts a detrimental impact on salivary gland tissues.<\/jats:p>","DOI":"10.3390\/ijms232112997","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T04:35:17Z","timestamp":1666845317000},"page":"12997","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Interleukin-22 Exerts Detrimental Effects on Salivary Gland Integrity and Function"],"prefix":"10.3390","volume":"23","author":[{"given":"Jing","family":"Zhou","sequence":"first","affiliation":[{"name":"The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0673-3400","authenticated-orcid":false,"given":"Shoko","family":"Onodera","sequence":"additional","affiliation":[{"name":"The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA"},{"name":"Department of Biochemistry, Tokyo Dental College, 2-9-18 Kanda Misaki-chou, Chiyoda-ku, Tokyo 101-0061, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Hu","sequence":"additional","affiliation":[{"name":"The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Yu","sequence":"additional","affiliation":[{"name":"The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA"},{"name":"Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00005-009-0002-4","article-title":"Sjogren\u2019s syndrome: An old tale with a new twist","volume":"57","author":"Lee","year":"2009","journal-title":"Arch. 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