Dr. Schett has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Amgen, Schering-Plough, Abbott, UCB, and Roche.
Treg cells suppress osteoclast formation: A new link between the immune system and bone
Version of Record online: 29 NOV 2007
Copyright © 2007 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 56, Issue 12, pages 4104–4112, December 2007
How to Cite
Zaiss, M. M., Axmann, R., Zwerina, J., Polzer, K., Gückel, E., Skapenko, A., Schulze-Koops, H., Horwood, N., Cope, A. and Schett, G. (2007), Treg cells suppress osteoclast formation: A new link between the immune system and bone. Arthritis & Rheumatism, 56: 4104–4112. doi: 10.1002/art.23138
- Issue online: 29 NOV 2007
- Version of Record online: 29 NOV 2007
- Manuscript Accepted: 31 AUG 2007
- Manuscript Received: 25 APR 2007
- Intramural ELAN grant from the University of Erlangen-Nuremberg
- German Research Community (DFG). Grant Number: Training grant GK592
- Sonderforschungsbereich. Grant Number: 643 Project B08
- START Program award from the Austrian Ministry of Sciences
To investigate whether Treg cells can suppress osteoclast differentiation, and to define a new potential link between the immune system and the skeleton.
Regulatory CD4+,CD25+,Foxp3+ T cells were isolated and purified from the spleen and cocultured with CD11b+ osteoclast precursor cells isolated from bone marrow. Osteoclastogenesis and bone erosion were assessed by tartrate-resistant acid phosphatase staining and pit resorption assay, respectively. In addition, Transwell experiments and cytokine-blocking experiments were performed to define the mechanisms of interaction between Treg cells and osteoclasts.
CD4+,CD25+,Foxp3+ T cells, but not CD4+,CD25− T cells, dose dependently inhibited macrophage colony-stimulating factor– and RANKL-dependent osteoclast formation. Pit formation was inhibited by up to 80% when Treg cells were added. The blockade of osteoclast formation was not based on the alteration of RANKL/osteoprotegerin balance but was essentially dependent on direct cell–cell contact via CTLA-4. Treg cell–mediated expression of transforming growth factor β, interleukin-4 (IL-4), and IL-10 contributed but was not essential to the inhibitory effect on osteoclastogenesis.
These data show that CD4+,CD25+,Foxp3+ Treg cells suppress osteoclast formation, provide a new link between the immune system and bone, and extend our knowledge on regulation of bone homeostasis by the immune system.