Extracellular vesicles mediate intercellular communication: Transfer of functionally active microRNAs by microvesicles into phagocytes
Extracellular vesicles mediate intercellular communication: Transfer of functionally active microRNAs by microvesicles into phagocytes
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DOI：
10.1002/eji.201646595
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发表时间：
2017-09-01
影响因子：
5.4
通讯作者：
Schiller, Martin
中科院分区：
文献类型：
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作者：
Classen, Laura;Tykocinski, Lars-Oliver;Schiller, Martin
细胞活化和凋亡导致细胞外囊泡（EV）如外来体或微囊泡（MV）的形成。EV已被证明可以调节免疫反应;最近，MV被描述为携带微小RNA（miRNA），并且已经讨论了MV在自身免疫性疾病发病机制中的作用。在这里，我们系统地根据它们的释放刺激表征MV和外来体。分析存活或凋亡的人T淋巴细胞和相应MV的miRNA含量。在EV吞噬后测量人单核细胞的miRNA、蛋白质和表面标记物表达以及细胞因子释放。最后，将健康个体与系统性红斑狼疮（SLE）患者的T淋巴细胞和MV中的miRNA表达进行比较。我们证明，根据刺激，不同亚型的EV被释放，大小不同，携带特定的RNA谱。我们观察到在诱导细胞凋亡和通过MV将功能性miRNA转移到人单核细胞中后，MV中不同miRNA的积累。从凋亡细胞释放的MV比从活细胞释放的MV引起更少的炎症反应。与健康个体相比，SLE患者T淋巴细胞和相应MV中的MiR-155*、miR-34 b和miR-34 a水平失调。
Cell activation and apoptosis lead to the formation of extracellular vesicles (EVs) such as exosomes or microvesicles (MVs). EVs have been shown to modulate immune responses; recently, MVs were described to carry microRNA (miRNA) and a role for MVs in the pathogenesis of autoimmune diseases has been discussed. Here we systematically characterized MVs and exosomes according to their release stimuli. The miRNA content of viable or apoptotic human T lymphocytes and the corresponding MVs was analyzed. miRNA, protein and surface marker expression, as well as cytokine release by human monocytes was measured after EV engulfment. Finally, miRNA expression in T lymphocytes and MVs of healthy individuals was compared with those of systemic lupus erythematosus (SLE) patients. We demonstrate that, depending on the stimuli, distinct subtypes of EVs are released, differing in size and carrying a specific RNA profile. We observed an accumulation of distinct miRNAs in MVs after induction of apoptosis and the transfer of functional miRNA by MVs into human monocytes. MVs released from apoptotic cells provoke less of an inflammatory response than those released from viable cells. MiR-155*, miR-34b and miR-34a levels in T lymphocytes and corresponding MVs were deregulated in SLE when compared to healthy individuals.