Stem Cell Laboratory, Department of Medical Sciences, University of Torino Torino, Italy.
Front Cell Dev Biol. 2016 Aug 22;4:83. doi: 10.3389/fcell.2016.00083. eCollection 2016.
Extra-cellular vesicles (EVs) are bilayer membrane structures enriched with proteins, nucleic acids, and other active molecules and have been implicated in many physiological and pathological processes over the past decade. Recently, evidence suggests EVs to play a more dichotomic role in the regulation of the immune system, whereby an immune response may be enhanced or supressed by EVs depending on their cell of origin and its functional state. EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) immune responses, as Ag carriers or presenters, or as vehicles for delivering active signaling molecules. On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by carrying immuno-modulatory effectors, such as transcriptional factors, non-coding RNA (Species), and cytokines. In addition, stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation, differentiation, and proliferation of B cells. They have been shown to control natural killer cell activity and to suppress the innate immune response (IIR). Studies reporting the role of EVs on T lymphocyte modulation are controversial. Discrepancy in literature may be due to stem cell culture conditions, methods of EV purification, EV molecular content, and functional state of both parental and target cells. However, mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. In this review, we will discuss how stem cell-derived EVs may contribute toward the modulation of the immune response. Collectively, stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system.
细胞外囊泡 (EVs) 是双层膜结构，富含蛋白质、核酸和其他活性分子，在过去十年中被认为与许多生理和病理过程有关。最近的证据表明，EVs 在免疫系统的调节中起着更为二分的作用，即 EV 可以根据其来源细胞及其功能状态增强或抑制免疫反应。例如，源自抗原 (Ag) 呈递细胞的 EV 已参与先天和获得性 (或适应性) 免疫反应，作为 Ag 载体或呈递者，或作为传递活性信号分子的载体。另一方面，肿瘤和干细胞衍生的 EV 已被确定通过携带免疫调节效应物，如转录因子、非编码 RNA (物种) 和细胞因子，对免疫反应发挥抑制作用。此外，据报道，干细胞衍生的 EV 还会损害树突状细胞的成熟，并调节 B 细胞的激活、分化和增殖。它们被证明可以控制自然杀伤细胞的活性并抑制先天免疫反应 (IIR)。报告 EV 对 T 淋巴细胞调节作用的研究存在争议。文献中的差异可能是由于干细胞培养条件、EV 纯化方法、EV 分子含量以及亲本和靶细胞的功能状态不同所致。然而，间充质干细胞衍生的 EV 被证明通过将 T 细胞从激活状态转变为 T 调节表型来发挥更具抑制性的作用。在这篇综述中，我们将讨论干细胞衍生的 EV 如何有助于调节免疫反应。总的来说，干细胞衍生的 EV 主要对免疫系统表现出抑制作用。
