Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis
Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis
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DOI：
10.1242/jcs.074088
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发表时间：
2011-02-01
影响因子：
4
通讯作者：
Simons, Mikael
中科院分区：
文献类型：
--
作者：
Fitzner, Dirk;Schnaars, Mareike;Simons, Mikael
少突胶质细胞向免疫细胞的抗原转移参与了自身免疫性疾病的发病机制。在这里，我们展示了少突胶质细胞分泌被称为外体的小膜泡，这些小泡在体外和体内都被小胶质细胞特异性地和有效地摄取。外切体的内化是通过大吞噬机制进行的，不会引起伴随的炎症反应。在干扰素-γ刺激小胶质细胞后，我们观察到小胶质细胞亚群中MHC-II类分子的上调。然而，外切体优先内化在似乎没有抗原提呈能力的小胶质细胞中。我们认为，小胶质细胞亚群对外切体的结构性大吞噬清除是小胶质细胞以免疫沉默的方式参与少突胶质细胞膜降解的重要机制。通过指定巨噬细胞吞噬能力和抗原呈递给不同的细胞，降解和免疫功能可能被分配给不同亚型的小胶质细胞。
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-gamma, 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.