宫颈癌HPV分型与Th17和Treg细胞的相关性研究

摘要

目的：检测感染人乳头状瘤病毒（human papilloma virus，HPV）患者的外周血中CD4+IL17+Th17、CD4+CD25+Foxp3+Treg细胞，分析Th17/Treg比值，比较血清中IL-17、IL-10、TGF-β、IL-23细胞因子的表达差异。方法：收集2014年9月至2016年6月119例新疆医科大学第一附属医院HPV感染未行治疗患者的资料，分为宫颈癌（cervical cancer，CC）组46例、宫颈上皮内瘤变（cervical intraepithelial neoplasia，CIN）Ⅱ～Ⅲ组43例、慢性宫颈炎（chronic cervicitis，CCS）组30例，根据检测HPV分型将患者HPV感染分为高危型80例与低危型39例，流式细胞仪检测Treg及Th17细胞，ELISA检测相关细胞因子。结果：高危型HPV感染患者中CC组感染率为87％（40/46），显著高于CINⅡ～Ⅲ组77%（33/43）及CCS组23%（7/30）。CC组外周血中Th17、Treg细胞及血清中相关细胞因子均明显高于其他两组，且随着宫颈病变加重，Th17/Treg比值升高更加显著。高危型HPV感染患者外周血中Th17和Treg细胞高于低危型HPV感染患者（P<0.05），Th17/Treg比值在高危型HPV感染患者中显著升高。高危型HPV感染患者血清中IL-17、IL-10、TGF-β、IL-23细胞因子的表达较低危型HPV感染患者均显著增高（P<0.05）。结论：Treg、Th17细胞在高危型HPV感染患者中存在增高现象，Th17/Treg比值的升高可能直接参与宫颈HPV的感染及免疫逃逸过程，在宫颈癌的发生发展中起着重要作用。%Objective:Based on the detection of CD4+IL17+Th17 and CD4+CD25+Foxp3+Treg cells in the peripheral blood of patients with human papilloma virus (HPV), the study analyzes the ratio of Th17 to Treg and compares the different expression of cytokine IL-17, IL-10, TGF-β, and IL-23 in the serum. Methods:From September 2014 to June 2016, 119 cases of untreated patients with cervical HPV in-fection were collected at the First Affiliated Hospital of Xinjiang Medical University, which include 46 cases of cervical cancer (CC), 43 cases with cervical intraepithelial neoplasia (CIN)Ⅱ-Ⅲ, and 30 with chronic cervicitis (CCS). The detection of HPV types classified 80 patients as high-risk and 39 as low-risk. Flow cytometry examined Treg and Th17 cells, and enzyme-linked immune sorbent assay was used to test related cytokines. Results:In the infection of high-risk cervical HPV, the rate of the CC group was 87%(40/46), which was higher than that of the CINⅡ-Ⅲgroup and the CCS group, which were 77%(33/43) and 23%(7/30), respectively. For the expression of Th17 and Treg cells in the peripheral blood and the related cytokine IL-17, IL-23, TGF-β, and IL-10 in the serum, the levels of CC group were also significantly higher than that of the other two groups, and the ratio of Th17 to Treg increased considerably with the se-verity of cervical lesions. The expression of Th17 and Treg cells in the peripheral blood of patients with high-risk cervical HPV were higher than that of patients with low-risk cervical HPV (P<0.05), which was the same for the expression of the related cytokine IL-17, IL-23, TGF-β, and IL-10 in the serum. The ratio of the Th17 to Treg of patients with high-risk cervical HPV increased remarkably (P<0.05). Conclusion:The expression of Treg and Th17 cells in high-risk patients exhibits an increasing trend, and the ratio of increased Th17 to Treg may directly participate in the process of HPV infection and immune evasion, which plays an important role in the occurrence and development of cervical cancer.