Zhang Zhiren, Zhang Zhi-Yuan, Fauser Uwe, Schluesener Hermann J
Institute of Brain Research, University of Tuebingen, Tuebingen, Germany.
Exp Neurol. 2009 Mar;216(1):75-82. doi: 10.1016/j.expneurol.2008.11.014. Epub 2008 Dec 3.
T-regulatory cells expressing the forkhead box transcription factor 3 (Foxp3) play essential roles in immune homeostasis. Experimental autoimmune neuritis (EAN) is an autoantigen-specific T-cell-mediated disease model for human demyelinating inflammatory disease of the peripheral nervous system. We investigated the distribution of Foxp3(+) cells in sciatic nerves, spleen and lymph nodes of EAN rats, and the influence of FTY720 on the localization of Foxp3(+) cells in EAN rats. In sciatic nerves of EAN rats, accumulation of Foxp3(+) cells was not seen during the pre-symptomatic phase (until Day 9) or during early or peak disease activity. In contrast, Foxp3(+) cell accumulation was regularly seen in the recovery from neurologic disease, suggesting a contribution of Foxp3(+) cells to the resolution of EAN. FTY720 was given at onset of EAN (Day 10) until Day 18. Following FTY720 administration, percentages of Foxp3(+) cells in EAN rats were increased in circulating blood, but reduced in lymph nodes compared to the PBS control. FTY720 treatment suppressed total numbers but increased percentages of Foxp3(+) cells in sciatic nerves of EAN rats. These data not only suggests a protective role of Foxp3(+) cells in EAN but also provides a potential way to alter localization of Foxp3(+) cells in vivo.
表达叉头框转录因子3（Foxp3）的调节性T细胞在免疫稳态中发挥着重要作用。实验性自身免疫性神经炎（EAN）是一种针对人类外周神经系统脱髓鞘炎性疾病的自身抗原特异性T细胞介导的疾病模型。我们研究了EAN大鼠坐骨神经、脾脏和淋巴结中Foxp3（+）细胞的分布，以及FTY720对EAN大鼠中Foxp3（+）细胞定位的影响。在EAN大鼠的坐骨神经中，在症状前期（直到第9天）或疾病活动早期或高峰期均未观察到Foxp3（+）细胞的积聚。相反，在神经疾病恢复过程中经常可见Foxp3（+）细胞积聚，这表明Foxp3（+）细胞对EAN的消退有作用。在EAN发病时（第10天）给予FTY720直至第18天。给予FTY720后，与PBS对照组相比，EAN大鼠循环血液中Foxp3（+）细胞的百分比增加，但淋巴结中的百分比降低。FTY720治疗抑制了EAN大鼠坐骨神经中Foxp3（+）细胞的总数，但增加了其百分比。这些数据不仅表明Foxp3（+）细胞在EAN中具有保护作用，还提供了一种在体内改变Foxp3（+）细胞定位的潜在方法。
