- Paper Report
- Open Access
IFN? production by activated T cells blocks osteoclastogenesis
- Willis Huang1
© Biomed Central Ltd 2001
- Received: 12 March 2001
- Accepted: 26 July 2001
- Published: 26 July 2001
RANKL (receptor activator of nuclear factor [NF]-?B ligand)-activated T-cells have been implicated as a potent source of osteoclastogenic stimulation, causing bone resorption in autoimmune arthritis and other chronic inflammatory conditions. However, T cells do not exclusively activate osteoclasts; cytokines produced by activated T cells have also been shown to inhibit osteoclast formation (see Additional information ). In this paper, Takayanagi et al show that interferon (IFN)-? produced by CD3-activated T cells inhibits osteoclastogenesis and that this inhibition results from accelerated degradation of TRAF6.
Several in vivo and in vitro experiments together convincingly demonstrated that IFN-? inhibits osteoclastogenesis. In vivo, IFN-? receptor knockout (IFN-?R -/-) mice had substantially less lipopolysaccharide (LPS)-stimulated calvarial bone resorption than wild-type mice. In vitro, osteoclast development was inhibited when activated T cells were added to stimulated bone marrow macrophage (BMM) cultures; this inhibitory effect was eliminated when anti-IFN-? antibody was concomitantly added. Stimulated BMMs from IFN-?R -/- mice formed osteoclasts even in the presence of activated T cells. Finally, direct addition of IFN-? to stimulated BMMs mimicked the inhibition of osteoclastogenesis seen with activated T cells. The intracellular signalling adaptor protein TRAF6 was found to be degraded in response to IFN-?, and constitutive expression of TRAF6 by retroviral infection rendered BMMs immune to the inhibitory effects of IFN-? on osteoclastogenesis.
Osteoclast cultures, immunoblots, immunoprecipitation
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