The different immunoregulatory functions on dendritic cells between mesenchymal stem cells derived from bone marrow of patients with low-risk or high-risk myelodysplastic syndromes.
The different immunoregulatory functions on dendritic cells between mesenchymal stem cells derived from bone marrow of patients with low-risk or high-risk myelodysplastic syndromes.
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低危和高危骨髓增生异常综合征患者骨髓间充质干细胞对树突状细胞的免疫调节功能不同。
DOI：
10.1371/journal.pone.0057470
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhao Z
中科院分区：
文献类型：
--
作者：
Wang Z;Tang X;Xu W;Cao Z;Sun L;Li W;Li Q;Zou P;Zhao Z
骨髓增生异常综合征（MDS）是一组进展性、克隆性、肿瘤性骨髓疾病，其特征为造血干细胞失调以及免疫系统异常。间充质干细胞（MSC）似乎在免疫应答的最初阶段通过抑制树突状细胞（DC）的分化和成熟来调节免疫系统。然而，MSC对DC发育的影响是否会因疾病状态而改变仍不清楚。此外，低危和高危MDS - MSC对DC发育的影响是否存在差异也不明确。在本研究中，我们的数据证实MDS - MSC对DC的分化有强烈的抑制作用。此外，MDS - MSC极大地改变了DC的功能，包括胞吞作用、白细胞介素 - 12（IL - 12）分泌以及它们抑制T细胞增殖的能力。而且，我们的结果显示低危和高危MDS - MSC在DC发育和功能方面存在重大差异。与高危MDS - MSC相比，低危MDS - MSC抑制DC分化和成熟的能力较弱；相应地，其DC胞吞功能障碍较轻，IL - 12分泌轻度减少，以及DC介导的对T细胞增殖的抑制作用降低。最后，我们的结果表明MDS - MSC衍生的转化生长因子 - β1（TGF - β1）在很大程度上是造成这些抑制作用的原因。这些结果阐明了MSC在低危和高危MDS中对DC发育的不同免疫调节作用，这对于理解MDS的发病机制以及开发治疗MDS的新型免疫疗法可能具有重要意义。
Myelodysplastic syndrome (MDS) is a group of progressive,clonal, neoplastic bone marrow disorders characterized by hematopoietic stem cell dysregulation and abnormalities in the immune system. Mesenchymal stem cells (MSC) appear to modulate the immune system at the very first step of the immune response through the inhibition of dendritic cells (DCs) differentiation and maturation. However, it is still unclear whether the effects of MSC on the development of DCs will be altered with disease state. In addition, it is not clear whether there are differences in the effects between low-risk and high-risk MDS-MSC on DCs development. In this study, our data confirm that MDS-MSC mediate a potent inhibition of DCs differentiation. Additionaly, MDS-MSC greatly alter DCs functions, including endocytosis, IL-12 secretion, their ability to inhibit T cell proliferation. Moreover, our results show that there are major differences in DCs development and function between low-risk and high-risk MDS-MSC. Compared to high-risk MDS-MSC, low-risk MDS-MSC is characterized by a poor ability to inhibit DCs differentiation and maturation; and correspondingly, less dysfunctional DC endocytosis, mildly decreased IL-12 secretion, and a reduction in DC-mediated inhibition of T cell proliferation. Finally, our results demonstrate that MDS-MSC derived TGF-β1 is largely responsible for the inhitory effects. These results elucidate the different immunoregulatory role of MSC in low-risk and high-risk MDS on DCs development, which may be important for understanding the pathogenesis of MDS and the development of novel immune therapies for the treatment of MDS.
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影响因子：
6.5
作者：
Alfinito, Fiorella;Sica, Michela;Terrazzano, Giuseppe
通讯作者：
Terrazzano, Giuseppe
影响因子：
5.2
作者：
Djouad, Farida;Charbonnier, Louis-Marie;Noel, Daniele
通讯作者：
Noel, Daniele
DOI：
10.1196/annals.1386.024
发表时间：
2006-01-01
期刊：
ESTROGENS AND HUMAN DISEASES
影响因子：
--
作者：
Buck, Miriam B.;Knabbe, Cornelius
通讯作者：
Knabbe, Cornelius
影响因子：
2.6
作者：
Guo, H;Fang, BJ;Zhao, RCH
通讯作者：
Zhao, RCH
影响因子：
6.2
作者：
Tse, WT;Pendleton, JD;Guinan, EC
通讯作者：
Guinan, EC