Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0708419 on July 29, 2009

Published online before print July 29, 2009
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(Journal of Leukocyte Biology. 2009;86:933-940.)
© 2009 Society for Leukocyte Biology

Regulation of dendritic cell survival and cytokine production by osteoprotegerin

Takahiro Chino*,1, Kevin E. Draves{dagger} and Edward A. Clark{dagger},{ddagger}

* Department of Oral Biology, School of Dentistry, and Departments of
{dagger} Microbiology and
{ddagger} Immunology, School of Medicine, University of Washington, Seattle, Washington, USA

1. Correspondence: Department of Oral Biology, University of Washington, Box 357132, 1959 NE Pacific St., Seattle, WA 98195-7132, USA. E-mail: tchino{at}washington.edu

ABSTRACT

The TNF family ligand, RANKL, and its two TNFR family receptors, RANK and OPG, enable coordinated regulation between the skeletal and immune systems. Relatively little is known about how OPG influences RANKL-RANK interactions for the regulation of DCs. Here, we show that OPG KO bone marrow-derived DCs survive better and produce more TNF-{alpha}, IL-12p40, and IL-23 in response to Escherichia coli LPS than WT DCs. RANKL is induced on DCs within 24 h after LPS stimulation. OPG limits RANKL-RANK interactions between DCs, which can promote DC survival and elevated expression of proinflammatory cytokines. Survival of and cytokine production by OPG KO DCs are inhibited by soluble OPG; conversely, anti-OPG enhances survival and cytokine production by WT DCs. Bim KO DCs, like OPG KO, also survive longer and produce more TNF-{alpha} than WT DCs; however, unlike OPG KO, Bim KO DCs do not produce more IL-23. In addition, after inoculation with LPS, OPG KO mice produce more TNF-{alpha} and IL-12p40 than WT mice but not more IL-6. Thus, OPG regulates not only DC survival but also the nature of DC-dependent inflammatory responses.

Key Words: inflammation • anti-inflammation • lifespan