{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:32:48Z","timestamp":1790127168647,"version":"4.0.1"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Periodontitis is an inflammatory disease driven by opportunistic bacteria including <jats:italic>Porphyromonas gingivalis<\/jats:italic> and <jats:italic>Fusobacterium nucleatum<\/jats:italic>, where T\u2010cell and NKT\u2010cell responses to these bacteria in patients with periodontitis grade B or C are not fully elucidated. The objective is to determine if exaggerated proinflammatory Th\u2010cell responses to periodontitis\u2010associated bacteria, but not commensal bacteria, is a characteristic of increased periodontitis grade.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mononuclear cells from patients with periodontitis grade C (<jats:italic>n<\/jats:italic>\u2009=\u200926) or grade B (<jats:italic>n<\/jats:italic>\u2009=\u200933) and healthy controls (HCs; <jats:italic>n<\/jats:italic>\u2009=\u200926) were stimulated with <jats:italic>P. gingivalis<\/jats:italic>, <jats:italic>F. nucleatum<\/jats:italic> or the commensal bacteria, <jats:italic>Staphylococcus epidermidis<\/jats:italic> and <jats:italic>Cutibacterium acnes.<\/jats:italic> Cytokine production by different T\u2010cell populations and FOXP3\u2010expression by regulatory T cells were assessed by flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to HCs, grade C patients had decreased frequencies of interleukin (IL)\u201010\u2010producing CD4+ T cells before stimulation (<jats:italic>p<\/jats:italic>\u2009=\u2009.02) and increased frequencies of IFN\u2010y\u2010producing CD4+ T cells after stimulation with <jats:italic>P. gingivalis<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009=\u2009.0019). Grade B patients had decreased frequencies of FOXP3+ CD4+ T cells before (<jats:italic>p<\/jats:italic>\u2009=\u2009.030) before and after stimulation with anti\u2010CD2\/anti\u2010CD3\/anti\u2010CD28\u2010loaded beads (<jats:italic>p<\/jats:italic>\u2009=\u2009.047), <jats:italic>P.\u00a0gingivalis<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009=\u2009.013) and <jats:italic>S. epidermidis<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009=\u2009.018). Clinical attachment loss correlated with the frequencies of IFN\u2010y\u2010producing Th1 cells in <jats:italic>P. gingivalis<\/jats:italic>\u2010 and <jats:italic>F. nucleatum<\/jats:italic>\u2010stimulated cultures in grade B patients (<jats:italic>p<\/jats:italic>\u2009=\u2009.023 and <jats:italic>p<\/jats:italic>\u2009=\u2009.048, respectively) and with the frequencies of Th17 cells in <jats:italic>P. gingivalis<\/jats:italic>\u2010stimulated cultures (<jats:italic>p<\/jats:italic>\u2009=\u2009.0062) in grade C patients. Patients with periodontitis grade C or grade B showed lower frequencies of IL\u201010\u2010producing NKT cells than HCs in unstimulated cultures (<jats:italic>p<\/jats:italic>\u2009=\u2009.0043 and <jats:italic>p<\/jats:italic>\u2009=\u2009.027 respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Both periodontitis groups showed decreased frequencies of immunoregulatory T\u2010cell and NKT cell subsets at baseline. Clinical attachment loss correlated with <jats:italic>P. gingivalis\u2010<\/jats:italic>induced Th17\u2010responses in grade C patients and with Th1\u2010responses in grade B patients when cells were stimulated with <jats:italic>P. gingivalis<\/jats:italic>, supporting that dysregulated pro\u2010inflammatory T\u2010cell responses to periodontitis\u2010associated bacteria contribute to the pathogenesis of periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.13317","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T09:27:53Z","timestamp":1720085273000},"page":"177-188","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cytokine responses of <scp>CD4<\/scp>+ T cells and <scp>NKT<\/scp> cells to periodontitis\u2010associated bacteria in individuals with or without periodontitis"],"prefix":"10.1111","volume":"60","author":[{"given":"Anne Katrine","family":"Danielsen","sequence":"first","affiliation":[{"name":"Research Area Periodontology, Section for Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Institute for Inflammation Research, Center for Rheumatology and Spine Diseases Rigshospitalet, Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5647-4617","authenticated-orcid":false,"given":"Laura","family":"Massarenti","sequence":"additional","affiliation":[{"name":"Research Area Periodontology, Section for Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Institute for Inflammation Research, Center for Rheumatology and Spine Diseases Rigshospitalet, Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"Minculescu","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Rigshospitalet, Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter \u00d8strup","family":"Jensen","sequence":"additional","affiliation":[{"name":"Institute for Inflammation Research, Center for Rheumatology and Spine Diseases Rigshospitalet, Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Department of Immunology and Microbiology Costerton Biofilm Center, University of Copenhagen Faculty of Health and Medical Sciences  Copenhagen Denmark"},{"name":"Department of Clinical Microbiology Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Riis","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Herlev and Gentofte Hospital, University of Copenhagen  Hellerup Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palle","family":"Holmstrup","sequence":"additional","affiliation":[{"name":"Research Area Periodontology, Section for Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2394-746X","authenticated-orcid":false,"given":"Christian","family":"Damgaard","sequence":"additional","affiliation":[{"name":"Research Area Periodontology, Section for Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Institute for Inflammation Research, Center for Rheumatology and Spine Diseases Rigshospitalet, Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus Henrik","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Research Area Periodontology, Section for Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Institute for Inflammation Research, Center for Rheumatology and Spine Diseases Rigshospitalet, Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,4]]},"reference":[{"issue":"3","key":"e_1_2_12_2_1","first-page":"235","article-title":"Pathogenesis of inflammatory periodontal disease. 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