The Interleukin-17 Receptor Plays a Gender-Dependent Role in Host Protection against Porphyromonas gingivalis -Induced Periodontal Bone Loss Article (Web of Science)

abstract

  • ABSTRACT Interleukin-17 (IL-17) is a proinflammatory 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 that are susceptible to neutrophils. Periodontal disease (PD) is a chronic inflammatory condition initiated by anaerobic oral pathogens such as Porphyromonas gingivalis , and it 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 levels have been found in humans with severe PD, we recently reported that female C57BL/6J 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 (J. J. Yu, M. J. Ruddy, G. C. Wong, C. Sfintescu, P. J. Baker, J. B. Smith, R. T. Evans, and S. L. Gaffen, Blood 109 :3794-3802, 2007). 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 immunoglobulin G and the chemokines KC/Groα and MIP-2. In contrast, male mice produced normal levels of chemokines and anti- P. gingivalis antibodies, but they were defective in granulocyte colony-stimulating factor upregulation. This study demonstrates a gender-dependent effect of IL-17 signaling and indicates that gender differences should be taken into account in the preclinical and clinical safety testing of anti-IL-17 biologic therapies.

authors

  • Yu, Jeffrey J.
  • Ruddy, Matthew J.
  • Conti, Heather R
  • Boonanantanasarn, Kanitsak
  • Gaffen, Sarah L.

publication date

  • 2008

webpage

published in

number of pages

  • 7

start page

  • 4206

end page

  • 4213

volume

  • 76

issue

  • 9