{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:19:20Z","timestamp":1792214360355,"version":"4.4.0"},"reference-count":15,"publisher":"National Academy of Sciences","issue":"25","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK097948)"],"award-info":[{"award-number":["DK097948)"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,23]]},"abstract":"<jats:p>\n                    TL1A and its receptor DR3 are key regulators of mucosal immune responses, but their role in periodontal disease is unknown. Herein, we investigated whether TL1A\/DR3 signaling contributes to mucosal immune amplification and tissue-destructive inflammation in periodontitis using SAMP1\/YitFc (SAMP) mice, which develop spontaneous ileitis and periodontal disease. DR3 deficiency markedly attenuated alveolar bone loss and improved periodontal architecture, restoring a phenotype comparable to healthy AKR (parental) controls. Gingival tissues from wild-type SAMP mice exhibited increased expression of both\n                    <jats:italic toggle=\"yes\">Tnfsf15<\/jats:italic>\n                    (encoding TL1A) and\n                    <jats:italic toggle=\"yes\">Tnfrsf25<\/jats:italic>\n                    (encoding DR3), with both positively correlating with disease severity. This was accompanied by elevated levels of IL-17, TNF-\u03b1, and IL-1\u03b2, and by increased numbers of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T helper cells and neutrophils. Conversely, SAMPxDR3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice exhibited reduced inflammatory cytokine production and immune cell accumulation. These findings support a model in which the TL1A\/DR3 axis is associated with amplification of mucosal immune responses in periodontal disease, linking effector T cell activation, increased cytokine production, and recruitment of innate immune cells. Altogether, our data identify the TL1A\/DR3 cytokine-receptor pair as a potential regulator of inflammatory circuits that drive periodontal pathology. Blocking this pathway may provide a therapeutic modality for patients affected by chronic periodontitis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2611178123","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T18:09:31Z","timestamp":1781806171000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["TL1A\/DR3 signaling deletion attenuates mucosal inflammation and alveolar bone loss in a murine model of spontaneous periodontitis"],"prefix":"10.1073","volume":"123","author":[{"given":"Sara","family":"Di Nicolantonio","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/051fd9666","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Case Western Reserve University School of Medicine","place":["Cleveland"]},{"id":[{"id":"https:\/\/ror.org\/01j9p1r26","id-type":"ROR","asserted-by":"publisher"}],"name":"Dental Unit, Department of Clinical Medicine, Public Health, Life and Environmental Sciences, University of L\u2019Aquila, Piazzale Salvatore Tommasi","place":["L\u2019Aquila, Italy"]},{"name":"Digestive Health Research Institute, Department of Medicine, Case Western Reserve University, School of Medicine","place":["Cleveland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8296-1888","authenticated-orcid":false,"given":"Maria R.","family":"Miranda","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/051fd9666","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Case Western Reserve University School of Medicine","place":["Cleveland"]},{"name":"Digestive Health Research Institute, Department of Medicine, Case Western Reserve University, School of 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Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Monaco","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01j9p1r26","id-type":"ROR","asserted-by":"publisher"}],"name":"Dental Unit, Department of Clinical Medicine, Public Health, Life and Environmental Sciences, University of L\u2019Aquila, Piazzale Salvatore Tommasi","place":["L\u2019Aquila, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8779-088X","authenticated-orcid":false,"given":"Paola","family":"Menghini","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/051fd9666","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Case Western Reserve University School of Medicine","place":["Cleveland"]},{"id":[{"id":"https:\/\/ror.org\/01j9p1r26","id-type":"ROR","asserted-by":"publisher"}],"name":"Dental Unit, Department of Clinical Medicine, Public Health, Life and 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