The characteristics and immunoregulatory functions of regulatory dendritic cells induced by mesenchymal stem cells derived from bone marrow of patient with chronic myeloid leukaemia.
The characteristics and immunoregulatory functions of regulatory dendritic cells induced by mesenchymal stem cells derived from bone marrow of patient with chronic myeloid leukaemia.
复制标题
DOI：
10.1016/j.ejca.2011.11.003
复制
发表时间：
2012-08
影响因子：
8.4
通讯作者：
Zhi-gang Zhao;Wen-xin Xu;Li Sun;Weiming Li;Qiubai Li;P. Zou
中科院分区：
文献类型：
--
作者：
Zhi-gang Zhao;Wen-xin Xu;Li Sun;Weiming Li;Qiubai Li;P. Zou
树突状细胞（dc）是一种特殊的抗原呈递细胞，在免疫应答的启动和调节中起着至关重要的作用。最近，间充质干细胞（MSCs）在T细胞甚至dc之间复杂的相互作用中显示出免疫调节作用后，得到了进一步的关注。然而，MSCs诱导dc的这些免疫调节作用的机制尚不清楚。此外，目前尚不清楚MSCs的免疫调节功能是否在疾病状态下发生改变。在这项研究中，我们发现慢性髓性白血病（CML）患者骨髓源性间充质干细胞（CML - msc）可以将成熟的DC （mDCs）分化为一个不同的调节性DC群体，它们具有较低的CD40、CD80、CD83和CD86表达。与未成熟的dc （imDCs）类似，CML-MSC诱导的dc （CML-MSC - DCs）表现出强大的吞噬能力。此外，CML-MSC-DCs具有诱导T细胞能量的能力，这是调节性DCs的另一种能力。CML-MSC-DCs不仅可以通过TGF-β1抑制T细胞的增殖，还可以诱导Treg细胞或T细胞能量的产生。最后，CML-MSC-DCs能够在体外诱导CD4+CD25 - Foxp3 - T细胞中更多的CD4+CD25+Foxp3+Tregs。基于敲低研究，CML-MSC-DCs衍生的TGF-β1主要负责CD4+CD25+Foxp3+Tregs的增加。CML-MSCs诱导的dc的免疫调节作用增强了自体MSCs在细胞治疗中的潜在应用。
Dendritic cells (DCs) are specialised antigen-presenting cells that play crucial roles in the initiation and regulation of immune responses. Recently, mesenchymal stem cells (MSCs) have gained further interest after demonstration of immunomodulatory effects on complicated interactions between T cells and even DCs. However, the mechanisms underlying these immunoregulatory effects of MSCs induced DCs are poorly understood. In addition, it is unclear whether the immunoregulatory functions of MSCs are altered in disease states. In this study, we showed that chronic myeloid leukaemia (CML) patients bone marrow derived MSCs (CML–MSC) could differentiate mature DCs (mDCs) into a distinct regulatory DC population, they had lower expression of CD40, CD80, CD83 and CD86. Similar to immature DCs (imDCs), CML–MSC induced DCs (CML–MSC–DCs) displayed powerful phagocytic capacity. Moreover, CML–MSC–DCs had the capacity to induce T cell anergy, another capacity of regulatory DCs. CML–MSC–DCs could inhibit the proliferation of T cells not only through TGF-β1, but also by inducing the production of Treg cells or T-cell anergy. At last, CML–MSC–DCs could efficiently induce more CD4+CD25+Foxp3+Tregs from naive CD4+CD25−Foxp3−T cells than that of normal-MSC–DCs in vitro. CML–MSC–DCs derived TGF-β1 was largely responsible for the increase in CD4+CD25+Foxp3+Tregs based on knockdown studies. The immunoregulatory effects of DCs induced by CML–MSCs enhance the potential use of autologous MSCs in cell therapy.