{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:10:21Z","timestamp":1790097021465,"version":"4.0.1"},"reference-count":156,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Periodontitis is a chronic immune-mediated inflammatory disease of the oral cavity, frequently linked to systemic conditions through complex immunological pathways. Regulatory T lymphocytes (Tregs) are pivotal in maintaining immune homeostasis by producing anti-inflammatory mediators and enforcing self-tolerance. Recent research has highlighted their role in inflammatory, immune-mediated, and neoplastic diseases. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, exploring the role of Tregs in periodontitis, including patients with comorbidities such as type 2 diabetes mellitus, rheumatoid arthritis, atherosclerosis, and cancer, with a focus on cytokine profile alterations and therapeutic implications of Treg modulation. A systematic search of PubMed, Scopus, Web of Science, and Cochrane from January 2015 to August 2025 using \u201cperiodontitis\u201d and \u201cTregs\u201d or \u201cregulatory T cells\u201d yielded 20 studies. Available evidence suggests alterations in the balance between immunomodulatory Tregs and pro-inflammatory Th17 lymphocytes, together with changes in related cytokine profiles compared with healthy controls. Changes in Treg-related immune markers have also been reported following periodontal interventions; however, these findings do not establish a causal role for Treg modulation or support Treg-targeted therapies in current clinical practice. Well-designed prospective studies and, where appropriate, randomized controlled trials are required to strengthen causal and therapeutic inference.<\/jats:p>","DOI":"10.3390\/ijms27188415","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:32:12Z","timestamp":1790083932000},"page":"8415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Regulatory T Cells in Periodontitis With or Without Systemic Diseases: A Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"given":"Angelo Michele","family":"Inchingolo","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Celeste","family":"Fatone","sequence":"additional","affiliation":[{"name":"Presidio Territoriale di AssistenzaTrani-ASL BT, Viale Padre Pio, 76125 Trani, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9163-2350","authenticated-orcid":false,"given":"Grazia","family":"Marinelli","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1494-3519","authenticated-orcid":false,"given":"Laura","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5374-7429","authenticated-orcid":false,"given":"Francesca","family":"Cal\u00f2","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3288-490X","authenticated-orcid":false,"given":"Andrea","family":"Palermo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3518-130X","authenticated-orcid":false,"given":"Marco","family":"Severino","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3797-5883","authenticated-orcid":false,"given":"Francesco","family":"Inchingolo","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6366-1039","authenticated-orcid":false,"given":"Alessio Danilo","family":"Inchingolo","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5947-8987","authenticated-orcid":false,"given":"Gianna","family":"Dipalma","sequence":"additional","affiliation":[{"name":"Department of Life Science, Health and Health Professional, Link Campus University, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1111\/j.1753-4887.2012.00493.x","article-title":"Defining the Human Microbiome","volume":"70","author":"Ursell","year":"2012","journal-title":"Nutr. 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