Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: The aims of the present study were to investigate the role played by natural killer T (NKT) cells in osteoclastogenesis and their effects on inflammatory bone destruction.
Methods: Patients with RA (n=25) and healthy controls (n=12) were enrolled in this study. In vitro osteoclastogenesis experiments were performed using peripheral blood mononuclear cells (PBMCs) in the presence of M-CSF and receptor activator of nuclear factor kB ligand (RANKL). PBMCs were cultured in vitro with α-galactosylceramide (αGalCer), and proliferation indices of NKT cells were estimated by flow cytometry. In vivoeffects of αGalCer-stimulated NKT cells on inflammation and bone destruction were determined in collagen-induced arthritis (CIA) mice.
Results: In vitroosteoclastogenesis was found to be significantly inhibited by αGalCer in healthy controls, but not in RA patients. Proliferative responses of NKT cells and STAT-1 phosphorylation in monocytes in response to αGalCer were impaired in RA patients. Notably, αGalCer-stimulated NKT cells inhibited osteoclastogenesis mainly via interferon-g production, in a cytokine-dependent manner (not by cell-cell contact), and down-regulated osteoclast-associated genes. αGalCer-treated mice showed less severe arthritis and reduced bone destruction. Moreover, proinflammatory cytokine expression in arthritic joints was found to be reduced by αGalCer treatment.
Conclusion: This study primarily demonstrates that αGalCer-stimulated NKT cells have a regulatory effect on osteoclastogenesis and a protective effect on inflammatory bone destruction. However, it also shows that these effects of αGalCer are diminished in RA patients, and that this is related to NKT cell dysfunction. These findings provide important information for those searching for novel therapeutic strategies to prevent bone destruction in RA.
To cite this abstract in AMA style:Kee SJ, Jin HM, Kang JH, Cho YN, Park KJ, Jung HJ, Park YW. Dysregulated Osteoclastogenesis Is Related to Natural Killer T Cell Dysfunction in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/dysregulated-osteoclastogenesis-is-related-to-natural-killer-t-cell-dysfunction-in-rheumatoid-arthritis/. Accessed January 25, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dysregulated-osteoclastogenesis-is-related-to-natural-killer-t-cell-dysfunction-in-rheumatoid-arthritis/