Chemokine signaling in myasthenia gravis and multiple sclerosis

我们研究了重症肌无力和多发性硬化患者淋巴细胞中的趋化因子信号。胸腺瘤重症肌无力患者外周血CD4+ T细胞中Th1型趋化因子信号显著改变，而胸腺增生患者Th1和Th2型趋化因子信号均改变。趋化因子CCL21的mRNA水平选择性增加，在增生的胸腺，而不是从正常胸腺或胸腺瘤获得的胸腺细胞中，CCL21的细胞迁移显着增强。另一种名为CCL19的CCR7配体的表达在正常胸腺、增生胸腺和胸腺瘤中相似。由于CCL 21在淋巴细胞和树突状细胞归巢至淋巴器官和B细胞活化中起关键作用，因此肥大胸腺中CCL 21表达升高与伴有胸腺增生的重症肌无力患者的免疫异常有因果关系。多发性硬化患者脑脊液T细胞Th1型趋化因子受体表达显著升高。复发期CSF中CCR5阳性的CD4+ T细胞数量一过性升高。相反，在复发期和缓解期获得的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一种有前途的方法来治疗重症肌无力和多发性硬化症患者。

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.