{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:10:35Z","timestamp":1788793835935,"version":"build-2803163510"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DE029436"],"award-info":[{"award-number":["DE029436"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370981"],"award-info":[{"award-number":["32370981"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Interleukin (IL)-22 mediates immune cell communication with nonhematopoietic cells and was shown to exert protective or destructive effects in different disease contexts. In the oral mucosal disease periodontitis, IL-22 has been associated with increased tissue destruction, although cause-and-effect evidence and the underlying mechanisms are lacking. Here, we showed that endogenous IL-22 was required for experimental periodontitis in mice, whereas local administration of exogenous IL-22 exacerbated periodontal inflammation and bone loss. Importantly, the ability of IL-22 to induce expression of inflammatory cytokines and tissue-degrading metalloproteinases as well as cause bone loss required intact IL-17 function, suggesting a potential cooperation between the two cytokines. As human fibroblasts prominently coexpress IL-22 and IL-17 receptors in the periodontal tissue and play a role in the pathogenesis of periodontitis, we examined them in vitro as potential targets of a destructive IL-22\u2013IL-17 interplay. IL-22 synergized with IL-17 for enhanced nuclear factor \u03baB\u2013mediated inflammatory responses (IL-6, matrix metalloproteinase-1) in a STAT3-dependent manner. Analysis of cytosolic and nuclear extracts revealed that IL-22 enhanced nuclear factor \u03baB p65 phosphorylation and translocation to the nucleus of IL-17\u2013stimulated fibroblasts. In conclusion, our study provides causal evidence for IL-22 involvement in periodontitis and describes a hitherto unknown IL-22\u2013IL-17 synergy in inflammatory bone loss.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag186","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:02:56Z","timestamp":1785517376000},"source":"Crossref","is-referenced-by-count":0,"title":["IL-22 synergizes with IL-17 to promote mucosal inflammation and bone loss"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7142-2386","authenticated-orcid":false,"given":"Xiaofei","family":"Li","sequence":"first","affiliation":[{"name":"Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University , Shanghai,","place":["China"]},{"name":"Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania , Philadelphia, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolan","family":"Ye","sequence":"additional","affiliation":[{"name":"Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5730-8802","authenticated-orcid":false,"given":"Xiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Liu","sequence":"additional","affiliation":[{"name":"Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0055-7357","authenticated-orcid":false,"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania , Philadelphia, PA,","place":["United States"]},{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University , Chengdu, Sichuan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M","family":"Korostoff","sequence":"additional","affiliation":[{"name":"Department of Periodontics, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania , Philadelphia, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gundappa","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania , Philadelphia, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Hyung","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania , Philadelphia, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7392-8852","authenticated-orcid":false,"given":"George","family":"Hajishengallis","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn 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