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Infection and Immunity, June 2005, p. 3453-3461, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3453-3461.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Gamma Interferon Positively Modulates Actinobacillus actinomycetemcomitans-Specific RANKL+ CD4+ Th-Cell-Mediated Alveolar Bone Destruction In Vivo

Yen-Tung A. Teng,1* Deeqa Mahamed,1 and Bhagirath Singh2

Division of Periodontics, Eastman Department of Dentistry, and Centre for Oral Biology, Department of Microbiology & Immunology, School of Medicine and Dentistry, the University of Rochester, Rochester, New York, 14620,1 Department of Microbiology & Immunology, School of Medicine and Dentistry, the University of Western Ontario, London, Ontario, N6A 5C1, Canada2

Received 5 November 2004/ Returned for modification 27 December 2004/ Accepted 26 January 2005

Recent studies have shown the biological and clinical significance of signaling pathways of osteogenic cytokines RANKL-RANK/OPG in controlling osteoclastogenesis associated with bone pathologies, including rheumatoid arthritis, osteoporosis, and other osteolytic disorders. In contrast to the inhibitory effect of gamma interferon (IFN-{gamma}) on RANKL-mediated osteoclastogenesis reported recently, alternative new evidence is demonstrated via studies of experimental periodontitis using humanized NOD/SCID and diabetic NOD mice and clinical human T-cell isolates from diseased periodontal tissues, where the presence of increasing IFN-{gamma} is clearly associated with (i) enhanced Actinobacillus actinomycetemcomitans-specific RANKL-expressing CD4+ Th cell-mediated alveolar bone loss during the progression of periodontal disease and (ii) a concomitant and significantly increased coexpression of IFN-{gamma} in RANKL(+) CD4+ Th cells. Therefore, there are more complex networks in regulating RANKL-RANK/OPG signaling pathways for osteoclastogenesis in vivo than have been suggested to date.

* Corresponding author. Mailing address: Lab. of Molecular Microbial Immunity, Eastman Dental Center, University of Rochester Medical Centre, Box 683, 625 Elmwood Ave., Rochester, NY 14620. Phone: (585) 275-7309. Fax: (585) 473-5254. E-mail: andy_teng{at}urmc.rochester.edu.

Editor: J. D. Clements

Infection and Immunity, June 2005, p. 3453-3461, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3453-3461.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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