{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:20:04Z","timestamp":1790742004678,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071123"],"award-info":[{"award-number":["82071123"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The aryl hydrocarbon receptor (AhR) has been studied as an intracellular pattern recognition receptor that can identify bacterial pigments. To identify a potential therapeutic target for periodontitis, we investigated the expression of AhR in periodontitis and its role in the pathogenesis of periodontitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>First, we analyzed AhR expression in a single\u2010cell dataset from human periodontal tissue. Quantitative polymerase chain reaction (qPCR), immunofluorescence, and immunohistochemistry were used to verify the AhR level. Later, we determined the phenotypes of ligature\u2010induced periodontitis in myeloid\u2010specific AhR\u2010deficient mice (Lyz2\u2010Cre<jats:sup>+\/\u2212<\/jats:sup> AhR<jats:sup>fx\/fx<\/jats:sup>), after which RNA sequencing (RNA\u2010seq), qPCR, Western blot, immunofluorescence, and immunohistochemistry were used to investigate the impacts of AhR on periodontitis and its mechanism. Finally, we determined the therapeutic effect of AhR agonist 6\u2010Formylindolo[3,2\u2010b]carbazole (FICZ) administration on murine periodontitis and verified the effects of FICZ on macrophage polarization in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AhR expression was enhanced in macrophages from periodontitis patients. Deletion of AhR from macrophages aggravated ligature\u2010induced periodontitis and promoted the inflammatory response. Calcium\/calmodulin\u2010stimulated protein kinase II (CaMKII) phosphorylation was accelerated in AhR\u2010deficient macrophages. Inhibiting CaMKII phosphorylation ameliorated periodontitis in Lyz2\u2010Cre<jats:sup>+\/\u2212<\/jats:sup> AhR<jats:sup>fx\/fx<\/jats:sup> mice. FICZ treatment blocked alveolar bone loss and relieved periodontal inflammation. FICZ diminished M1 macrophage polarization and promoted M2 macrophage polarization upon M1 macrophage induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>AhR played a protective role in the pathogenesis of periodontitis by orchestrating macrophage polarization via interacting with the CaMKII signaling pathway.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.24-0021","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T11:17:50Z","timestamp":1720178270000},"page":"67-81","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Beyond transcription, aryl hydrocarbon receptor plays a protective role in periodontitis by interacting with CaMKII"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0664-9789","authenticated-orcid":false,"given":"Xuwen","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of 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