{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:35:20Z","timestamp":1791272120584,"version":"4.1.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Increasing epidemiologic evidence supports a link between periodontitis and rheumatoid arthritis. The actual involvement of periodontitis in the pathogenesis of rheumatoid arthritis and the underlying mechanisms remain, however, poorly understood. We investigated the influence of concomitant periodontitis on clinical and histopathologic characteristics of T cell\u2013mediated experimental arthritis and evaluated modulation of type II collagen (CII)\u2013reactive Th cell phenotype as a potential mechanism. Repeated oral inoculations of periodontal pathogens Porphyromonas gingivalis and Prevotella nigrescens induced periodontitis in mice, as evidenced by alveolar bone resorption. Interestingly, concurrent periodontitis induced by both bacteria significantly aggravated the severity of collagen-induced arthritis. Exacerbation of arthritis was characterized by increased arthritic bone erosion, whereas cartilage damage remained unaffected. Both P. gingivalis and P. nigrescens skewed the CII-specific T cell response in lymph nodes draining arthritic joints toward the Th17 phenotype without affecting Th1. Importantly, the levels of IL-17 induced by periodontal pathogens in CII-specific T cells directly correlated with the intensity of arthritic bone erosion, suggesting relevance in pathology. Furthermore, IL-17 production was significantly correlated with periodontal disease\u2013induced IL-6 in lymph node cell cultures. The effects of the two bacteria diverged in that P. nigrescens, in contrast to P. gingivalis, suppressed the joint-protective type 2 cytokines, including IL-4. Further in vitro studies showed that the Th17 induction strongly depended on TLR2 expression on APCs and was highly promoted by IL-1. Our data provide evidence of the involvement of periodontitis in the pathogenesis of T cell\u2013driven arthritis through induction of Ag-specific Th17 response.<\/jats:p>","DOI":"10.4049\/jimmunol.1301970","type":"journal-article","created":{"date-parts":[[2014,3,29]],"date-time":"2014-03-29T01:29:22Z","timestamp":1396056562000},"page":"4103-4111","source":"Crossref","is-referenced-by-count":196,"title":["Periodontal Pathogens Directly Promote Autoimmune Experimental Arthritis by Inducing a TLR2- and IL-1\u2013Driven Th17 Response"],"prefix":"10.1093","volume":"192","author":[{"given":"Sabrina G","family":"de Aquino","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre , 6500 HB Nijmegen,","place":["The Netherlands"]},{"name":"Department of Diagnosis and Oral Surgery, Periodontic Division, Araraquara Dental School , Sao Paulo 14801,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahla","family":"Abdollahi-Roodsaz","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre , 6500 HB Nijmegen,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije I","family":"Koenders","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre , 6500 HB Nijmegen,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fons A J","family":"van de Loo","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre , 6500 HB Nijmegen,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ger J M","family":"Pruijn","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, Radboud University Nijmegen , 6500 HB Nijmegen,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renoud J","family":"Marijnissen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre , 6500 HB Nijmegen,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitte","family":"Walgreen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre , 6500 HB Nijmegen,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique M","family":"Helsen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre , 6500 HB Nijmegen,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liduine A","family":"van den Bersselaar","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre , 6500 HB Nijmegen,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael S","family":"de Molon","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Oral Surgery, Periodontic Division, Araraquara Dental School , Sao Paulo 14801,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario J Avila","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo , Sao Paulo 05508,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Q","family":"Cunha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine of Ribeirao Preto , Sao Paulo 14049,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joni A","family":"Cirelli","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Oral Surgery, Periodontic Division, Araraquara Dental School , Sao Paulo 14801,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim B","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre , 6500 HB Nijmegen,","place":["The 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