Treg cells suppress osteoclast formation:a new link between the immune system and bone

Zaiss, Mario M, Axmann, Roland, Zwerina, Jochen, Polzer, Karin, Gückel, Eva, Skapenko, Alla, Schulze-Koops, Hendrik, Horwood, Nikki ORCID:, Cope, Andrew and Schett, Georg (2007) Treg cells suppress osteoclast formation:a new link between the immune system and bone. Arthritis and Rheumatism, 56 (12). pp. 4104-4112. ISSN 0004-3591

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OBJECTIVE: To investigate whether Treg cells can suppress osteoclast differentiation, and to define a new potential link between the immune system and the skeleton. METHODS: 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. RESULTS: 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 beta, interleukin-4 (IL-4), and IL-10 contributed but was not essential to the inhibitory effect on osteoclastogenesis. CONCLUSION: 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.

Item Type: Article
Uncontrolled Keywords: animals,pharmacology,pharmacology,cytology,metabolism,ctla-4 antigen,physiology,drug effects,cells, cultured,female,metabolism,physiology,metabolism,pharmacology,mice,mice, inbred c57bl,cytology,physiology,cytology
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User: LivePure Connector
Date Deposited: 06 Mar 2019 11:30
Last Modified: 19 Oct 2023 02:23
DOI: 10.1002/art.23138

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