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Infect. Immun. doi:10.1128/IAI.01209-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The IL-17 receptor plays a gender-dependent role in host protection against P. gingivalis-induced periodontal bone loss

Department of Microbiology and Immunology, University at Buffalo, SUNY, Buffalo NY; Department of Oral Biology, University at Buffalo, SUNY, Buffalo NY

^* To whom correspondence should be addressed. Email: sgaffen{at}buffalo.edu.

	Abstract

IL-17 is a pro-inflammatory cytokine secreted by the newly-described CD4+ Th17 subset, which is distinct from classic Th1 and Th2 lineages. IL-17 contributes to bone destruction in rheumatoid arthritis, but is essential in host defense against pathogens susceptible to neutrophils. Periodontal disease (PD) is a chronic inflammatory condition initiated by anaerobic oral pathogens such as Porphyromonas gingivalis, and is characterized by host-mediated alveolar bone destruction due primarily to the immune response. The role of IL-17 in PD is controversial. Whereas elevated IL-17 has been found in humans with severe PD, we recently reported that female C57BL/6J (B6) mice lacking the IL-17 receptor (IL-17RA^KO) are significantly more susceptible to PD bone loss, due to defects in the chemokine-neutrophil axis (Yu et al., 2007. Blood 109:3794-3802). Since different mouse strains exhibit differences in susceptibility to PD as well as Th1/Th2 cell skewing, we crossed the IL-17RA gene knockout onto the BALB/C background and observed a similar enhancement in alveolar bone loss following P. gingivalis infection. Unexpectedly, in both strains IL-17RA^KO female mice were much more susceptible to PD bone loss than males. Moreover, female BALB/C-IL-17RA^KO mice were defective in producing anti-P. gingivalis IgG and the chemokines KC/Gro and MIP-2. In contrast, male mice produced normal levels of chemokines and anti-P. gingivalis Abs, but were defective in G-CSF upregulation. This study demonstrates a gender-dependent effect IL-17 signaling, and indicates that gender differences should be taken into account in pre-clinical and clinical safety testing of anti-IL-17 biologic therapies.