Apoptotic cell-derived membrane microparticles: molecular characterization, immunmodulatory activity and their role in the pathogenesis of systemic lupus erythematosus

细胞外囊泡的研究是一个非常年轻的科学领域。迄今为止，膜微粒被讨论介导细胞间通讯或作为免疫反应的调节剂。然而，这些囊泡的分子组成和膜微粒与应答细胞的相互作用仅部分了解。在过去的几年里，我们的小组和其他人可以提供证据表明，从凋亡细胞释放的膜囊泡不同于从活化/活细胞释放的膜囊泡。此外，这些亚细胞囊泡已被证明可以调节不同应答细胞的功能。还讨论了微粒在自身免疫性疾病发病机制中的作用。我们先前已经表明，参与系统性红斑狼疮（SLE）发病机制的自身抗原在凋亡细胞的孤立微粒内积累。除此之外，我们能够在凋亡细胞衍生的微粒内检测HMGB 1。直到最近，通过释放膜囊泡的遗传信息交换已经被讨论。基于我们以前的工作，我们希望在本项目中解决以下几点。 将进一步研究分离的膜微粒的分子组成。在这里，我们想比较从健康个体和SLE患者获得的分离的膜微粒。 将表征膜微粒和抗原呈递细胞（即树突细胞）之间的相互作用。3） 在用膜微粒刺激后，我们将分析抗原呈递细胞和它们的应答细胞之间的相互作用（即树突状细胞和淋巴细胞之间的相互作用）4） 将建立体内模型以研究分离的膜微粒的免疫调节作用。

Research on extracellular vesicles represents a very young field in science. To date, membrane microparticles are discussed to mediate intercellular communication or act as regulators of immune responses. However, the molecular composition of these vesicles and the interaction of membrane microparticles with responder cells are only partially understood. During the last years our group and others could provide evidence that membrane vesicles released from apoptotic cells differ from those released from activated/viable cells. Further, these subcellular vesicles have been shown to modulate the function of different responder cells. A role of microparticles in the pathogenesis of autoimmune diseases has also been discussed. We have previously shown, that autoantigens, which are involved in the pathogenesis of systemic lupus erythematosus (SLE) accumulate within isolated microparticles of apoptotic cells. Beside this we were able to detect HMGB1 within apoptotic cell derived microparticles. Only recently, the exchange of genetic information via released membrane vesicles has been discussed. Based on our previous work we want to address the following points within this project.1) The molecular composition of isolated membrane microparticles will be further investigated. Here, we want to compare isolated membrane microparticles obtained from healthy individuals and SLE patients.2) The interactions between membrane microparticles and antigen presenting cells (i.e. dendritic cells) will be characterized.3) After stimulation with membrane microparticles we will analyze the interactions between antigen presenting cells and their responder cells (i.e. interactions between dendritic cells and lymphocytes)4) An in vivo model will be established to investigate the immunomodulatory effects of isolated membrane microparticles.