Tang Wei, Lv Qian, Chen Xiang-fang, Zou Jun-jie, Liu Zhi-min, Shi Yong-quan
Department of Endocrinology, Shanghai Changzheng Hospital, Shanghai, PR China.
Cell Physiol Biochem. 2013;32(4):827-37. doi: 10.1159/000354485. Epub 2013 Sep 20.
Damage to Schwann cells has been reported in the development of diabetic peripheral neuropathy (DPN), but how Schwann cells are damaged has not been elucidated.
The highly expressed proteins in the PBMC of DPN patients were identified through MALDI-TOF/TOF and SELDI protein chip technology. The expression levels of CXCR3 were detected by qPCR and flow cytometric analysis. Transwell migration assay was to investigate the migration of CD8(+) T cells. Western-blot analysis was to detect the levels of p38 MAP kinases pathway related proteins and TNF-α, FasL, and PDL1.
Two highly expressed proteins, CXCR3 and p38, were identified. Under high glucose conditions, CXCR3 was elevated in CD8(+) T cells via the activation of p38 MAP kinases. Moreover, CXCL9, CXCL10, and CXCL11 expression were induced in Schwann cells, leading to the recruitment and infiltration of CD8(+) T cells into DPN tissues. Further study demonstrated that Schwann cells promoted activation of CD8(+) T cells and induced expression of TNF-α, FasL, and PDL1 on CD8(+) T cells, in return, CD8(+) T cells induced obvious apoptosis of Schwann cells.
Our study indicates that CD8(+) T cells mediate cytotoxicity toward Schwann cells and play an important role in the development of DPN.
糖尿病周围神经病变（DPN）的发展过程中已报道存在施万细胞损伤，但施万细胞如何受损尚未阐明。
通过基质辅助激光解吸电离飞行时间/串联飞行时间质谱（MALDI-TOF/TOF）和表面增强激光解吸电离（SELDI）蛋白质芯片技术鉴定DPN患者外周血单核细胞（PBMC）中高表达的蛋白质。采用实时定量聚合酶链反应（qPCR）和流式细胞术分析检测CXCR3的表达水平。采用Transwell迁移实验研究CD8(+) T细胞的迁移。蛋白质免疫印迹分析检测p38丝裂原活化蛋白激酶（MAP）信号通路相关蛋白以及肿瘤坏死因子-α（TNF-α）、Fas配体（FasL）和程序性死亡受体配体1（PDL1）的水平。
鉴定出两种高表达蛋白质，即CXCR3和p38。在高糖条件下，p38 MAP激酶激活导致CD8(+) T细胞中CXCR3升高。此外，施万细胞中诱导了CXCL9、CXCL10和CXCL11的表达，导致CD8(+) T细胞募集并浸润至DPN组织。进一步研究表明，施万细胞促进CD8(+) T细胞活化，并诱导CD8(+) T细胞表达TNF-α、FasL和PDL1，反过来，CD8(+) T细胞诱导施万细胞发生明显凋亡。
我们的研究表明，CD8(+) T细胞介导对施万细胞的细胞毒性作用，并在DPN的发展中起重要作用。
