Role of Sortilin in Models of Autoimmune Neuroinflammation
Role of Sortilin in Models of Autoimmune Neuroinflammation
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DOI：
10.4049/jimmunol.1403156
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发表时间：
2015-12-15
影响因子：
4.4
通讯作者：
Zipp, Frauke
中科院分区：
文献类型：
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作者：
Reuter, Eva;Weber, Juliane;Zipp, Frauke
前神经营养因子受体分拣蛋白是一种具有双重功能的蛋白质，参与细胞内蛋白质转运以及细胞信号转导。该受体与各种神经元疾病如痴呆、癫痫发作和脑损伤的相关性已得到充分证实。相比之下，对分拣蛋白在免疫细胞和炎症性疾病中的作用知之甚少。本研究的目的是阐明分拣蛋白在小鼠和人类不同免疫细胞类型中的分布，并分析其在自身免疫性CNS炎症中的功能。分拣蛋白在鼠和人巨噬细胞和树突细胞中表达最深，在B和T细胞中表达程度低得多。在树突状细胞中，分拣蛋白对Ag加工有影响。因此，分拣蛋白在患有多发性硬化症（CNS的最常见的炎性自身免疫性疾病）的患者的CNS中由浸润的血管周围骨髓细胞高度表达，主要在血管袖中。然而，分拣蛋白基因靶向小鼠（Sort 1（-/-））和嵌合体缺乏分拣蛋白在免疫系统中的野生型同窝出生的T细胞依赖性实验性自身免疫性脑脊髓炎的易感性。考虑到我们的研究结果和其他研究者的最新数据，我们得出结论，前神经营养因子受体分拣蛋白在先天性免疫过程中发挥作用，而不是在适应性免疫过程中发挥作用，因此，不是在自身免疫性神经炎症中发挥作用。
The proneurotrophin receptor sortilin is a protein with dual functions, being involved in intracellular protein transport, as well as cellular signal transduction. The relevance of the receptor for various neuronal disorders, such as dementia, seizures, and brain injury, is well established. In contrast, little is known about the role of sortilin in immune cells and inflammatory diseases. The aim of our study was to elucidate the distribution of sortilin in different immune cell types in mice and humans and to analyze its function in autoimmune CNS inflammation. Sortilin was expressed most profoundly in murine and human macrophages and dendritic cells and to a much lesser extent in B and T cells. In dendritic cells, sortilin had an impact on Ag processing. Accordingly, sortilin was highly expressed by infiltrated perivascular myeloid cells, mainly in vessel cuffs, in the CNS of patients suffering from multiple sclerosis, the most common inflammatory autoimmune disease of the CNS. Yet, sortilin gene-targeted mice (Sort1(-/-)) and chimeras deficient in sortilin in the immune system were as susceptible as wild-type littermates to T cell-dependent experimental autoimmune encephalomyelitis. Considering our results and recent data from other investigators, we conclude that the proneurotrophin receptor sortilin plays a role in innate, rather than in adaptive, immune processes and, thus, not in autoimmune neuroinflammation.