Extracellular Ubiquitin Enhances the Suppressive Effects of Regulatory T cells on Effector T cell Responses
Extracellular Ubiquitin Enhances the Suppressive Effects of Regulatory T cells on Effector T cell Responses
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DOI：
10.7754/clin.lab.2014.140314
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发表时间：
2014-01-01
影响因子：
0.7
通讯作者：
Xia, Rong
中科院分区：
文献类型：
--
作者：
Cao, Yuezhen;Li, Chengli;Xia, Rong
背景资料：CD 4（+）CD 25（+）FoxP 3（+）调节性T（Treg）细胞主要通过调节CD 4（+）CD 25（-）效应性T（Teff）细胞的功能，在免疫稳态，尤其是免疫耐受中发挥重要作用。由于Treg细胞活性的降低与自身免疫性疾病密切相关，因此调节Treg细胞活性的策略成为近年来研究的热点。方法：首先采用流式细胞术检测人外周血单个核细胞（PBMC）中Treg细胞与FITC标记的泛素的结合效率。使用transwell测定，我们评估了泛素对原代Treg细胞的趋化性迁移的影响。结果：原代Treg细胞与FITC标记的细胞外泛素之间存在明显的亲和性。此外，我们发现泛素对Treg细胞的趋化迁移具有增强作用。向Treg和Teff细胞的共培养物中添加泛素增强了Treg细胞对Teff细胞增殖的抑制作用。结论：细胞外Ub通过与Treg细胞直接结合，影响Treg细胞的调节功能，可能通过间接调控Teff细胞来调节免疫应答。
Background: CD4(+)CD25(+) FoxP3(+) Regulatory T (Treg) cells have been proven to play important roles in immune homeostasis, especially immune tolerance, mainly by regulating the function of CD4(+)CD25(-) effector T (Teff) cells. As the reduced activity of Treg cells is closely related with autoimmune diseases, development of strategies for modulating the activity of Treg cells has become the focus of recent studies.Methods: We first determined the binding efficiency of Treg cells in human peripheral blood mononuclear cells (PBMCs) to FITC-labeled ubiquitin by flow cytometry. Using transwell assays, we evaluated the effect of ubiquitin on chemotactic migration of primary Treg cells. By multi-parametric flow cytometry analysis, we analyzed the influence of extracellular ubiquitin on the regulatory function and the apoptosis of Treg cells.Results: We observed that primary Treg cells and FITC-labeled extracellular ubiquitin show affinity for each other. In addition, we found that ubiquitin exhibited an enhancing effect on chemotactic migration of Treg cells. The addition of ubiquitin to co-cultures of Treg and Teff cells enhanced the inhibitory effect of Treg cells on Teff cell proliferation. Moreover, the apoptosis of Treg cells could be reduced after ubiquitin treatment.Conclusions: We proved that extracellular Ub could significantly affect the regulatory function of Treg cells by binding directly to them and, thus, modulate the immune response probably through the indirect control of Teff cells.