Chemokine signaling in myasthenia gravis and multiple sclerosis

我们研究了重症肌无力合并多发性硬化症患者淋巴细胞中的趋化因子信号。重症肌无力合并胸腺瘤患者外周血CD4+ T细胞中th1型趋化因子信号明显改变，而胸腺增生性患者外周血中th1型和th2型趋化因子信号均发生改变。趋化因子CCL21的mRNA水平在增生性胸腺中选择性升高，CCL21的细胞迁移在增生性胸腺细胞中明显增强，而在正常胸腺和胸腺瘤中没有增强。另一种CCR7配体CCL19的表达在正常胸腺、增生性胸腺和胸腺瘤中相似。由于CCL21在淋巴细胞和树突状细胞向淋巴器官的归巢和B细胞活化中起关键作用，因此CCL21在增生性胸腺中的表达升高与重症肌无力合并胸腺增生患者的免疫异常有因果关系。多发性硬化症患者脑脊液（CSF） T细胞上th1型趋化因子受体表达显著升高。脑脊液中携带CCR5的CD4+ T细胞数量在复发期短暂升高。相比之下，在复发期和缓解期，CSF中具有另一种th1型受体CXCR3的CD4+ T细胞的数量仍然很高。这些数据表明，调节趋化因子信号是治疗重症肌无力和多发性硬化症患者的一种有希望的方法。

We studied chemokine signaling in lymphocytes of patients with myasthenia gravis and multiple sclerosis. Th1-type chemokine signaling in peripheral blood CD4+ T cells was significantly altered in myasthenia gravis patients with thymoma, while both Th1-and Th2-type chemokine signaling were altered in patients with hyperplasic thymus. The mRNA level for chemokine CCL21 was selectively increased in the hyperplasic thymuses, and cellular migration by CCL21 was markedly enhanced in thymocytes obtained from hyperplasic thymuses but not from normal thymuses or thymomas. The expression of another CCR7 ligand named CCL19 was similar among normal thymuses, hyperplasic thymuses, and thymomas. Since CCL21 plays a critical role in the homing of lymphocytes and dendritic cells to lymphoid organs and B cells activation, the elevated CCL21 expression in hyperplasic thymuses is causatively associated with the immune abnormalities of myasthenia gravis patients with thymic hyperplasia. Th1-type chemokine receptor expression on cerebrospinal fluid (CSF) T cells were significantly elevated in multiple sclerosis patients. The number of CD4+ T cells with CCR5 in CSF was transiently increased at relapse stage. In contrast, the number of CD4+ T cells with another Th1-type receptor CXCR3 remained high in the CSF obtained both at relapse stage and remission stage. These data suggest that modulation of chemokine signaling is a promising method to treat patients with myasthenia gravis and multiple sclerosis.