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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Periodontal Pathogens Directly Promote Autoimmune Experimental Arthritis by Inducing a TLR2-and IL-1-Driven Th17 Response

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de Aquino, Sabrina G. [1, 2] ; Abdollahi-Roodsaz, Shahla [1] ; Koenders, Marije I. [1] ; van de Loo, Fons A. J. [1] ; Pruijn, Ger J. M. [3] ; Marijnissen, Renoud J. [1] ; Walgreen, Birgitte [1] ; Helsen, Monique M. [1] ; van den Bersselaar, Liduine A. [1] ; de Molon, Rafael S. [2] ; Avila Campos, Mario J. [4] ; Cunha, Fernando Q. [5] ; Cirelli, Joni A. [2] ; van den Berg, Wim B. [1]
Total Authors: 14
[1] Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol Rheumatol Res & Adv Therapeut, NL-6500 HB Nijmegen - Netherlands
[2] Araraquara Dent Sch, Periodont Div, Dept Diag & Oral Surg, BR-14801 Sao Paulo - Brazil
[3] Radboud Univ Nijmegen, Dept Biomol Chem, NL-6500 HB Nijmegen - Netherlands
[4] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, BR-05508 Sao Paulo - Brazil
[5] Univ Sao Paulo, Dept Pharmacol, BR-14049 Sao Paulo - Brazil
Total Affiliations: 5
Document type: Journal article
Source: JOURNAL OF IMMUNOLOGY; v. 192, n. 9, p. 4103-4111, MAY 1 2014.
Web of Science Citations: 60

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-mediated experimental arthritis and evaluated modulation of type II collagen (CII)-reactive 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-induced 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-driven arthritis through induction of Ag-specific Th17 response. The Journal of Immunology, 2014, 192: 4103-4111. (AU)

FAPESP's process: 09/00341-7 - Association between rheumatoid arthritis and periodontal disease: evaluation of the IL-23/IL-17 axis
Grantee:Joni Augusto Cirelli
Support Opportunities: Regular Research Grants
FAPESP's process: 08/08142-0 - Evaluation of rheumatoid arthritis and periodontal disease association. Study of IL-23/IL-17 axis in experimental model of rheumatoid arthritis and periodontal disease in mice.
Grantee:Sabrina Garcia de Aquino
Support Opportunities: Scholarships in Brazil - Doctorate