The Cooperative Role of CCR1 and CCR5 in the Migration of Osteoclast Precursors and RANKL+ Cells Throughout Inflammatory Bone Loss after Periodontal Infection

Abstracts expression with siRNA. We concluded that the generation of these Th1-like Tregs was mediated by IFN-γ-T-bet pathway and the role of CD40-activated B cells in CD4+ T-cell differentiation was dependent on the strength of the activation to T cells. doi:10.1016/j.clim.2010.03.426

S.111. The Cooperative Role of CCR1 and CCR5 in the Migration of Osteoclast Precursors and RANKL+ Cells Throughout Inflammatory Bone Loss after Periodontal Infection Carlos Repeke 1, Samuel Fereira Jr 1, Ana Paula Trombone 3, Priscila Colavite 1, Francine Raimundo 1, Mario Avila-Campos 2, Joao Silva 3, Marcela Claudino 1, Gerson Assis 1, Gustavo Garlet 1. 1School of Dentistry of Bauru, Bauru, Brazil; 2Institute of Biomedical Sciences, Sao Paulo, Brazil; 3School of Medicine of Ribeirão Preto, Ribeirao Preto, Brazil Periodontal Disease (PD) is characterized by the inflammatory bone resorption in response to the bacterial challenge, in a host response that involves a series of chemokine and its receptors supposed to control cell influx into periodontal tissues and determine disease outcome. In this study, we investigated the role of chemokine receptors

S141 in the immunoregulation of experimental PD in mice. A. actinomycetemcomitans-infected C57Bl/6-WT mice developed an intense inflammatory reaction and severe alveolar bone resorption, associated with the migration of CCR5+, CCR1+ and RANKL+ cells to periodontal tissues. Interestingly, CCR5KO and CCR1KO mice strains presented a significant, but partial, reduction in the bone loss levels. High frequencies of CCR5+ CD3+RANKL+ and CCR1+CD3-RANKLwere found in periodontal lesions. CCR5 absence resulted decreased TNF-α, Il-1b, IFN-g and RANKL levels; and a reduction in the CD3+ and RANKL+ cells influx into periodontal tissues was verified. The lack of CCR1 presented a less pronounced effect over cytokine expression, being only a small reduction in the levels TNF-α and Il-1b verified; however, a significant reduction in the number of CD14+ cells was verified. The simultaneous CCR1/CCR5 inhibition by mAb treatment resulted in a more effective attenuation of PD progression associated with lower values of bone loss and decreased counts of leukocytes in periodontal tissues. Our results suggest that CCR1 may act as a chemmoatractant of osteoclast precursors to periodontal environment, while CCR5 attracts RANKL+ cells with osteoclastogenic properties. Therefore, our data demonstrate the cooperative role of such receptors in the inflammatory bone resorption process throughout experimental PD. doi:10.1016/j.clim.2010.03.427