Treg cells suppress osteoclast formation -: A new link between the immune system and bone
Treg cells suppress osteoclast formation -: A new link between the immune system and bone
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DOI：
10.1002/art.23138
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发表时间：
2007-12-01
影响因子：
--
通讯作者：
Schett, Georg
中科院分区：
文献类型：
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作者：
Zaiss, Mario M.;Axmann, Roland;Schett, Georg
Objective.为了研究Treg细胞是否可以抑制破骨细胞分化，并确定免疫系统和破骨细胞之间的新的潜在联系。从脾中分离和纯化调节性CD 4+、CD 25+、Foxp 3 + T细胞，并与从骨髓中分离的CD 11b+破骨细胞前体细胞共培养。采用抗酒石酸酸性磷酸酶染色法和陷窝吸收法检测破骨细胞生成和骨侵蚀情况，并通过Transwell实验和精氨酸阻断实验探讨Treg细胞与破骨细胞相互作用的机制。CD 4+、CD 25+、Foxp 3 + T细胞，而不是CD 4+、CD 25- T细胞，剂量依赖性地抑制巨噬细胞集落刺激因子和RANKL依赖性破骨细胞的形成。当添加Treg细胞时，凹坑形成被抑制高达80%。破骨细胞形成的阻断不是基于RANKL/骨保护素平衡的改变，而是基本上依赖于通过CTLA-4的直接细胞-细胞接触。Treg细胞介导的转化生长因子β、白细胞介素-4（IL-4）和IL-10的表达对破骨细胞生成的抑制作用有贡献，但不是必需的。这些数据表明，CD 4+、CD 25+、Foxp 3 + Treg细胞抑制破骨细胞形成，提供了免疫系统和骨之间的新联系，并扩展了我们对免疫系统调节骨稳态的认识。
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 cytokineblocking 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.