趋化因子及其受体在重症肌无力患者胸腺组织的异常表达

The abnormal expression and function of chemokines and their receptors in the thymus of patients with myasthenia gravis

本研究利用基因芯片方法筛选出MG患者和正常胸腺组织差异性表达的趋化因子,并采用趋化实验和流式细胞术观察MG患者胸腺组织提取液对胸腺细胞的趋化作用。基因芯片结果显示,有49种基因在MG患者和对照组胸腺组织表达量均低,有21种基因在MG和对照组胸腺呈显著表达;其中CCL3、CCL22、CCL25、CCR7、CCR9基因在MG患者胸腺表达显著高于对照组,CCL2、CX3CL1、CXCL10、CXCR6、IL-8基因在MG患者胸腺组织表达显著低于对照组。趋化实验显示,MG胸腺提取液对CD8和CD4单阳性细胞的趋化作用,与正常人胸腺提取液相比,已发生明显变化。提示MG患者胸腺组织中存在趋化因子及其受体的表达异常可能通过对不同胸腺细胞亚群的趋化作用影响胸腺细胞的分化发育。

This article aims to compare the expression of chemokines and their receptors in thymus tissue of patients with myasthenia gravis（MG） and normal controls groups,and to investigate the abnormal expression and function of chemokines and their receptors in thymus of MG patients.By using the way of gene array,the chemokines expressed differently in thymus between MG patients and normal controls were screened.Then,the gene array results through the way of SYBR Green I real-time quantitative PCR about several chemokines and their receptors selected were verified.The chemotaxis function of the thymus tissue extract of MG patients to thymocytes was observed by using chemotaxis experiment and flow cytometry.It was found that the results of gene array showed that there were 49 genes with low expression and 21 genes with significant expression in both MG patients and normal controls,in which the expression levels of CCL3,CCL22,CCL25,CCR7 and CCR9 gene were significantly higher,while those of CCL2,CX3CL1,CXCL10,CXCR6 and IL-8 gene were significantly lower in MG patients than in normal controls.The results of SYBR Green I real-time quantitative PCR and gene array were fundamentally conformed.The chemotaxis experiments showed that MG thymus tissue extract had a stronger chemotactic effect to CD8＋ single positive thymocytes than any other types of thymocytes.Through this study it is evident that many kinds of chemokines exist in thymus tissues of MG patients with abnormal expression of their receptors mRNA and they may affect the differentiation and development of thymocytes through their chemotactic effect on different subsets of thymocytes.