Zhang Z-Y, Zhang Z, Schluesener H J
Institute of Brain Research, University of Tuebingen, Tuebingen, Germany.
Neuropathol Appl Neurobiol. 2009 Oct;35(5):487-95. doi: 10.1111/j.1365-2990.2009.01016.x. Epub 2009 Feb 4.
Experimental autoimmune neuritis (EAN) is a well-known animal model of human demyelinating polyneuropathies. Here we have studied the spatiotemporal accumulation of interleukin (IL)-17(+) cells in sciatic nerves of EAN rats and effects of FTY720, an agonist of sphingosine-1-phosphate (S1P) receptors.
In this study, we examined the spatiotemporal expression of IL-17 using immunohistochemistry and RT-PCR, and analysed the IL-17(+) cell proportion in blood and lymph nodes using flow cytometry.
In sciatic nerves of EAN rats, IL-17(+) cells were mainly found to concentrate around blood vessels and IL-17(+) cell accumulation was temporally correlated with severity of neurological signs. FTY720, which has been shown to reduce severity of EAN, attenuated accumulation of IL-17(+) cells in sciatic nerves, decreased IL-17(+) cell proportion in peripheral blood, but increased IL-17(+) cell proportion in lymph nodes, suggesting the involvement of S1P signal pathway in regulating IL-17(+) cell trafficking.
our data are consistent with the possibility that IL-17(+) cells might contribute to the pathogenesis of EAN and the S1P signal pathway may be involved in the in vivo trafficking of IL-17(+) cells.
实验性自身免疫性神经炎(EAN)是一种众所周知的人类脱髓鞘性多发性神经病动物模型。在此,我们研究了EAN大鼠坐骨神经中白细胞介素(IL)-17阳性细胞的时空积聚情况以及鞘氨醇-1-磷酸(S1P)受体激动剂FTY720的作用。
在本研究中,我们使用免疫组织化学和逆转录-聚合酶链反应检测了IL-17的时空表达,并使用流式细胞术分析了血液和淋巴结中IL-17阳性细胞的比例。
在EAN大鼠的坐骨神经中,主要发现IL-17阳性细胞聚集在血管周围,且IL-17阳性细胞的积聚与神经体征的严重程度在时间上相关。已证明可减轻EAN严重程度的FTY720减弱了坐骨神经中IL-17阳性细胞的积聚,降低了外周血中IL-17阳性细胞的比例,但增加了淋巴结中IL-17阳性细胞的比例,提示S1P信号通路参与调节IL-17阳性细胞的转运。
我们的数据支持IL-17阳性细胞可能参与EAN发病机制且S1P信号通路可能参与IL-17阳性细胞体内转运的可能性。