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

Journal article

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.

Authors: Zaiss, M; Axmann, R; Zwerina, J; Polzer, K; Gückel, E

• Publication status: Published
• Journal: Arthritis and rheumatism
• Volume: 56
• Issue: 12
• Pages: 4104-4112
• Publication date: 2007-12-01
• DOI: 10.1002/art.23138
• EISSN: 1529-0131
• ISSN: 0004-3591
• Language: English
• Keywords: Immune System; Mice; T-Lymphocytes, Regulatory; Antigens, CD; Forkhead Transcription Factors; Cell Communication; Macrophage Colony-Stimulating Factor; Cell Differentiation; Mice, Inbred C57BL; Bone and Bones; Female; Antigens, Differentiation; Animals; RANK Ligand; Cells, Cultured; Antigens, CD11; Osteoclasts; Interleukin-2 Receptor alpha Subunit; CTLA-4 Antigen