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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF IMMUNOLOGY; v. 192, n. 9, p. 4103-4111, MAY 1 2014.
• Citações Web of Science: 60

Resumo

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)

• Processo FAPESP: 08/08142-0 - Avaliação da associação entre a artrite reumatóide e a doença periodontal. Estudo do eixo IL-23/IL-17 em modelo experimental de artrite reumatóide e doença periodontal em camundongos.
• Beneficiário: Sabrina Garcia de Aquino
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 09/00341-7 - Associação entre artrite reumatóide e doença periodontal: avaliação do eixo IL-23/IL-17
• Beneficiário: Joni Augusto Cirelli
• Linha de fomento: Auxílio à Pesquisa - Regular