Zhou Liyu, Xu Feng, Chang Chunkang, Tao Ying, Song Luxi, Li Xiao
Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
Blood Coagul Fibrinolysis. 2016 Apr;27(3):301-7. doi: 10.1097/MBC.0000000000000423.
The present study was performed to investigate the role of interleukin-17-producing CD4-positive T cells in the pathogenesis of primary immune thrombocytopenia (ITP). Peripheral blood was collected from ITP patients and healthy controls. The immunophenotyping of T lymphocytes and the detection of T helper 1/2/17 (Th1/Th2/Th17) cells were performed by flow cytometry, Th1/Th2/Th17-associated cytokines were determined by cytokines microarray and ELISA. The association between Th17 and T regulatory cells (Tregs) was also investigated. The percentage of Th17 and Th1 cells were markedly increased in ITP patients especially in those with severe ITP compared with normal controls. Th17 cytokines microarray revealed the upregulation of proinflammatory cytokines and downregulation of inflammatory inhibitory cytokines in ITP patients compared with that in the normal controls. Further ELISA analysis verified high levels of Th17-associated proinflammatory cytokines such as interleukin-17A/F, interleukin-6 and interleukin-23 and low levels of inflammatory inhibitory factors including interleukin-10 and transforming growth factor-β in ITP patients compared with normal controls. We also observed that the ratio of Th17/Treg was significantly higher in severe ITP than that in mild ITP and normal controls and inversely correlated with platelet count. In addition, Tregs from ITP patients could suppress the secretion of interferon-γ by effector CD4-positive T cells, but had no effect on interleukin-17 production in vitro. Th17 cells are increased in ITP patients, and the inversion of Th17/Treg may contribute to the activation of autoimmunity.
本研究旨在探讨产生白细胞介素-17的CD4阳性T细胞在原发性免疫性血小板减少症（ITP）发病机制中的作用。收集ITP患者和健康对照者的外周血。通过流式细胞术进行T淋巴细胞免疫表型分析及辅助性T细胞1/2/17（Th1/Th2/Th17）细胞检测，采用细胞因子芯片和酶联免疫吸附测定法（ELISA）测定Th1/Th2/Th17相关细胞因子。同时研究Th17与调节性T细胞（Tregs）之间的关联。与正常对照相比，ITP患者尤其是重度ITP患者中Th17和Th1细胞的百分比显著增加。Th17细胞因子芯片显示，与正常对照相比，ITP患者促炎细胞因子上调，炎症抑制细胞因子下调。进一步的ELISA分析证实，与正常对照相比，ITP患者中Th17相关促炎细胞因子如白细胞介素-17A/F、白细胞介素-6和白细胞介素-23水平较高，而包括白细胞介素-10和转化生长因子-β在内的炎症抑制因子水平较低。我们还观察到，重度ITP患者中Th17/Treg比值显著高于轻度ITP患者和正常对照，且与血小板计数呈负相关。此外，ITP患者的Tregs可抑制效应性CD4阳性T细胞分泌干扰素-γ，但对体外白细胞介素-17的产生无影响。ITP患者中Th17细胞增加，Th17/Treg比值倒置可能有助于自身免疫激活。
