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

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/Groalpha 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: Jeffrey J Yu, Matthew J Ruddy, Heather R Conti, Kanitsak Boonanantanasarn, Sarah L Gaffen
• Journal: Infection and immunity (Infect Immun) Vol. 76 Issue 9 Pg. 4206-13 (Sep 2008) ISSN: 1098-5522 [Electronic] United States
• PMID: 18591228 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bacterial
• Chemokine CXCL1
• Chemokine CXCL2
• Immunoglobulin G
• Receptors, Interleukin-17
• Granulocyte Colony-Stimulating Factor

Topics

• Alveolar Bone Loss (immunology, pathology)
• Animals
• Antibodies, Bacterial (immunology)
• Bacteroidaceae Infections (immunology, pathology)
• Chemokine CXCL1 (biosynthesis)
• Chemokine CXCL2 (biosynthesis)
• Female
• Granulocyte Colony-Stimulating Factor (biosynthesis)
• Humans
• Immunoglobulin G (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Porphyromonas gingivalis (immunology)
• Receptors, Interleukin-17 (deficiency, immunology)
• Sex Factors