Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis.
Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis.
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DOI：
10.1186/s13287-016-0304-5
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发表时间：
2016-03-17
影响因子：
7.5
通讯作者：
Ballester S
中科院分区：
文献类型：
--
作者：
Bravo B;Gallego MI;Flores AI;Bornstein R;Puente-Bedia A;Hernández J;de la Torre P;García-Zaragoza E;Perez-Tavarez R;Grande J;Ballester A;Ballester S
多发性硬化症是一种广泛存在的炎症性脱髓鞘疾病。有几种免疫调节疗法可用，包括干扰素-β、醋酸格拉替雷、那他珠单抗、芬戈莫德和米托蒽醌。尽管它们对延缓疾病进展有用，但它们不能提供确定的治愈，并且与一些不期望的副作用相关。因此，寻找新的治疗方法构成了一个活跃的研究领域。使用间充质干细胞（MSC）来改变疾病进程是目前非常感兴趣的主题。蜕膜来源的间充质干细胞（DMSC）是从人胎盘胚外膜获得的能够分化成三个胚层的细胞群。本研究探讨了DMSCs的治疗潜力。我们使用实验性自身免疫性脑脊髓炎（EAE）动物模型来评估DMSC对疾病临床体征和中枢神经系统中炎性浸润存在的影响。我们还比较了DMSC治疗小鼠与EAE对照动物脾T细胞的炎症特征，以及DMSC对体外Th 17表型定义的影响。此外，我们分析了对中枢神经系统浸润中一些关键细胞类型存在的影响。预防性腹膜内注射DMSC导致EAE的外部体征显著延迟。此外，对已经出现中度症状的动物进行治疗导致轻度EAE，疾病评分降低。除炎性浸润减少外，在治疗动物的浸润物中发现CD 4 + IL 17+、CD 11b + Ly 6 G+和CD 11b + Ly 6C+细胞的百分比减少。早期免疫应答减轻，DMSC处理的小鼠的脾细胞显示出对抗原的低增殖应答，白细胞介素（IL）-17的产生减少，抗炎细胞因子IL-4和IL-10的产生增加。此外，在DMSC处理的小鼠中检测到较低的RORγT和较高的加塔-3表达水平。DMSC还显示出对Th 17表型的体外定义的不利影响。DMSC调节EAE的临床过程，改变疾病期间中枢神经系统浸润的频率和细胞组成，并介导有利于Th 2亚型的Th 17表型建立的损害。这些结果表明，DMSCs可能提供一种新的基于细胞的治疗多发性硬化症的控制。本文的在线版本（doi：10.1186/s13287-016-0304-5）包含补充材料，可供授权用户使用。
Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. Accordingly, the search for new therapeutic methods constitutes an active investigation field. The use of mesenchymal stem cells (MSCs) to modify the disease course is currently the subject of intense interest. Decidua-derived MSCs (DMSCs) are a cell population obtained from human placental extraembryonic membranes able to differentiate into the three germ layers. This study explores the therapeutic potential of DMSCs. We used the experimental autoimmune encephalomyelitis (EAE) animal model to evaluate the effect of DMSCs on clinical signs of the disease and on the presence of inflammatory infiltrates in the central nervous system. We also compared the inflammatory profile of spleen T cells from DMSC-treated mice with that of EAE control animals, and the influence of DMSCs on the in vitro definition of the Th17 phenotype. Furthermore, we analyzed the effects on the presence of some critical cell types in central nervous system infiltrates. Preventive intraperitoneal injection of DMSCs resulted in a significant delay of external signs of EAE. In addition, treatment of animals already presenting with moderate symptoms resulted in mild EAE with reduced disease scores. Besides decreased inflammatory infiltration, diminished percentages of CD4+IL17+, CD11b+Ly6G+ and CD11b+Ly6C+ cells were found in infiltrates of treated animals. Early immune response was mitigated, with spleen cells of DMSC-treated mice displaying low proliferative response to antigen, decreased production of interleukin (IL)-17, and increased production of the anti-inflammatory cytokines IL-4 and IL-10. Moreover, lower RORγT and higher GATA-3 expression levels were detected in DMSC-treated mice. DMSCs also showed a detrimental influence on the in vitro definition of the Th17 phenotype. DMSCs modulated the clinical course of EAE, modified the frequency and cell composition of the central nervous system infiltrates during the disease, and mediated an impairment of Th17 phenotype establishment in favor of the Th2 subtype. These results suggest that DMSCs might provide a new cell-based therapy for the control of multiple sclerosis. The online version of this article (doi:10.1186/s13287-016-0304-5) contains supplementary material, which is available to authorized users.