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小窝胞饮作用介导少突胶质细胞来源的外泌体向小胶质细胞的选择性转移

Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis.

机构信息

Max-Planck Institute for Experimental Medicine, Hermann-Rein-Str., D-37075 Göttingen, Germany.

出版信息

J Cell Sci. 2011 Feb 1;124(Pt 3):447-58. doi: 10.1242/jcs.074088.

DOI:10.1242/jcs.074088
PMID:21242314
Abstract

The transfer of antigens from oligodendrocytes to immune cells has been implicated in the pathogenesis of autoimmune diseases. Here, we show that oligodendrocytes secrete small membrane vesicles called exosomes, which are specifically and efficiently taken up by microglia both in vitro and in vivo. Internalisation of exosomes occurs by a macropinocytotic mechanism without inducing a concomitant inflammatory response. After stimulation of microglia with interferon-γ, we observe an upregulation of MHC class II in a subpopulation of microglia. However, exosomes are preferentially internalised in microglia that do not seem to have antigen-presenting capacity. We propose that the constitutive macropinocytotic clearance of exosomes by a subset of microglia represents an important mechanism through which microglia participate in the degradation of oligodendroglial membrane in an immunologically 'silent' manner. By designating the capacity for macropinocytosis and antigen presentation to distinct cells, degradation and immune function might be assigned to different subtypes of microglia.

摘要

少突胶质细胞向免疫细胞转移抗原已被认为与自身免疫性疾病的发病机制有关。在这里,我们表明少突胶质细胞分泌小膜囊泡,称为外泌体,它们在体外和体内都被小胶质细胞特异性和有效地摄取。外泌体的内化通过巨胞饮作用机制发生,而不会引起伴随的炎症反应。在用干扰素-γ刺激小胶质细胞后,我们观察到小胶质细胞中 MHC Ⅱ类的上调。然而,外泌体优先被似乎没有抗原呈递能力的小胶质细胞内化。我们提出,小胶质细胞亚群中组成性的巨胞饮清除外泌体代表了一个重要的机制,通过该机制,小胶质细胞以免疫“沉默”的方式参与少突胶质细胞膜的降解。通过将巨胞饮作用和抗原呈递的能力指定给不同的细胞,降解和免疫功能可能被分配给不同的小胶质细胞亚型。

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