Study on the correlation between the expression of PD-1on Treg cells of peripheral blood and Foxp3, TGF-beta and IL-10 in patients with cystic echinococcosis
ZHAO Hui1, ZHANG Feng-bo1, ZHU Yue-jie1, PANG Nan-nan1, AN Meng-ting2, LI Bin2, MA Xiu-min1, DING Jian-bing1, 2
1. The first affiliated hospital, Xinjiang MedicalUniversity, Urumqi 830011, China; 2. Collage of Basic medicine, Xinjiang Medical University, Urumqi 830011, China
Abstract：To investigate the relationship between negative costimulatory molecule PD-1 and Treg cells in cystic echinococcosis and their roles in the occurrence and development of the disease, by detecting the expression of PD-1 on Treg cells and Treg cell-related factors Foxp3, TGF-beta and IL-10 in peripheral blood of patients with cystic echinococcosis. Flow cytometry was used to detect the proportion of PD-1+CD4+CD25+Treg cells in peripheral blood of 30 patients with cystic echinococcosis and 30 healthy controls. The expressions of PD-1 and Foxp3 in peripheral blood mononuclear cells were detected by real-time fluorescence quantitative PCR. The serum levels of TGF-beta and IL-10 were detected by ELISA and the correlation between the expression of PD-1 and Foxp3, TGF-beta and IL-10 in peripheral blood of patients with cystic echinococcosis was analyzed by Pearson correlation method. Results showed that comparing with the control group, the proportion of PD-1+CD4+CD25+Treg cells in peripheral blood of patients with cystic echinococcosis increased significantly. The levels of PD-1 and Foxp3 in peripheral blood mononuclear cells increased significantly, while the levels of TGF-beta and IL-10 in serum increased significantly. The expressions of PD-1 and Foxp3 in peripheral blood of patients with cystic echinococcosis were positively correlated, while the levels of TGF-beta and IL-10 in PD-1+CD4+CD25+Treg cells were positively correlated. In conclusion, the high expression of negative costimulatory molecule PD-1 in Treg cells is related to the production and function of Treg cells and cytokines TGF-beta and IL-10, which may promote the sustained development of Echinococcus granulosus infection.
赵慧, 张峰波, 朱玥洁, 庞楠楠, 安梦婷, 李斌, 马秀敏, 丁剑冰. 囊性包虫病患者外周血PD-1在Treg细胞上的表达与Foxp3、TGF-β和IL-10的相关性研究[J]. 中国人兽共患病学报, 2020, 36(6): 475-480.
ZHAO Hui, ZHANG Feng-bo, ZHU Yue-jie, PANG Nan-nan, AN Meng-ting, LI Bin, MA Xiu-min, DING Jian-bing. Study on the correlation between the expression of PD-1on Treg cells of peripheral blood and Foxp3, TGF-beta and IL-10 in patients with cystic echinococcosis. Chinese Journal of Zoonoses, 2020, 36(6): 475-480.
[1] 温浩. 包虫病学[M]. 人民卫生出版社, 2015: 15-19. [2] Zhang FB, Pang NN, Zhu YJ,et al.CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells are positively correlated with levels of IL-21 in active and transitional cystic echinococcosis patients[J]. BMC Infect Dis, 2015,15(1):457. DOI: 10.1186/s12879-015-1156-9 [3] 刘晓霞,马海梅,朱明,等. 细粒棘球蚴egG1Y162疫苗对小鼠免疫应答的研究[J].中国人兽共患病学报, 2013, 29(3):226-231. DOI: 10.3969/j.issn.1002-2694.2013.03.004 [4] 徐岩,庞楠楠,郭忠帅,等. CD11C+CD45RA+髓样树突状细胞在泡球蚴感染小鼠中的水平变化[J].新疆医科大学学报, 2016, 39(5):565-568. DOI: 10.3969/j.issn.1009-5551.2016.05.010 [5] Zhang FB, Li SY, Zhu YJ, et al.Immunization of mice with egG1Y162-1/2 provides protection against Echinococcus granulosus infection in BALB/c mice[J]. Mol Immunol,2018, 9(94):183-189. DOI: 10.1016/j.molimm.2018.01.002 [6] La XL, Zhang FB, Li YH, et al.Upregulation of PD-1 on CD4+CD25+T cells is associated with immunosuppression in liver of mice infected with Echinococcus multilocularis[J]. Int Immunopharmacol, 2015,26(2):357-366. DOI: 10.1016/j.intimp.2015.04.013 [7] Yi M,Jiao DC,Xu HX, et al.Biomarkers for Predicting Efficacy of PD-1/PD-L1 Inhibitors[J]. Mol Cancer,2018, 17(1):129. DOI: 10.1186/s12943-018-0864-3 [8] Sharma M, Yang Z, Miyamoto H.Immunohistochemistry of immune checkpoint markers PD-1 and PD-L1 in prostate cancer[J]. Medicine (Baltimore), 2019, 98(38): e17257. DOI: 10.1097/MD.0000000000017257. [9] 庞盼, 张峰波,朱玥洁,等. 布鲁氏菌病患者中PD-1和PD-L1的表达[J]. 中国免疫学杂志, 2017, 33(12):1838-1842. DOI: 10.3969/j.issn.1000-484X.2017.12.017 [10] Pang NN, Zhang FB, Ma XM, et al.Effect of TGF-β/Smad signaling pathway on Th17 cells and Treg cells in Echinococcus multilocularis infection[J]. Int Immunopharmacol, 2014, 20(3):248-267. DOI: 10.1016/j.intimp.2014.02.038 [11] Gao M,Liu LX,Wu FL, et al. The changes of Th17/Treg and related cytokines: IL-17, IL-23, IL-10,TGF-β in respiratory syncytial virus bronchiolitis rat model[J]. Iran J Allergy Asthma Immunol,2017, 16(5): 386-395. PMID: 29149778 [12] 薛冰, 徐笛,张峰波,等. 血清IFN-γ、IL-4、IL-12、IL-23对肺结核免疫的作用研究[J].新疆医科大学学报, 2017, 40(3):341-345. DOI: 0.2017-03-019 [13] Li X,Su Y,Hua X, et al.Levels of hepatic Th17 cells and regulatory T cells upregulated by hepatic stellate cells in advanced HBV-related liver fibrosis[J]. J Transl Med,2017, 15(1):75. DOI: 10.1186/s12967-017-1167-y [14] Maj T,Wang W,Crespo J, et al.Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor[J]. Nat Immunol,2017, 18(12):1332-1341. DOI: 10.1038/ni.3868 [15] Shi L, Feng M, Du S, et al.Adenosine Generated by regulatory T cells induces CD8+ T cell exhaustion in gastric cancer through A2aR pathway[J]. Biomed Res Int, 2019,14:4093214. DOI: 10.1155/2019/4093214. [16] 陈媛,庞楠楠, 赵骁,等. 囊性包虫病患者Th9细胞相关细胞因子mRNA表达特点研究[J]. 国际检验医学杂志, 2019, 40(8):908-912. DOI: CNKI:SUN:GWSQ.0.2019-08-004 [17] 郭忠帅,张峰波,向阳,等.IL-18及IL-18结合蛋白、IFN-γ等血清炎性介质在囊型包虫病致 Th1/Th2细胞偏移中的意义[J].新疆医科大学学报, 2016, 39(4):430-432,436. DOI: CNKI:SUN:XJYY.0.2016-04-011 [18] 赵慧, 庞楠楠, 马海梅, 等. 泡球蚴感染小鼠Tregs与Th17细胞相关细胞因子的平衡变化[J]. 中国病原生物学杂志, 2012,7(2): 129-131. DOI:CNKI:SUN:IISC. 0.2012-02-016 [19] 赵慧,张峰波,庞楠楠,等. Tim-3/Galectin-9与Th1/Th2相关因子在人细粒棘球蚴感染中的表达研究[J].新疆医科大学学报,2016, 39(3): 312-315,319. DOI: 10.3969/j.issn.1009-5551.2016.03.012 [20] 郭声,陈娜,葛善飞,等. Th17/Treg平衡在乙型肝炎重症化过程中的作用及临床意义[J]. 2016, 24(5):341-346. DOI: 10.3760/cma.j.issn.1007-3418.2016.05.006 [21] Aparicio JL,Ottobre M,Duhalde Vega M, et al.Effects of interleukin 17A (IL-17A) neutralization on murine hepatitis virus (MHV-A59) infection[J]. Eur Cytokine Netw,2017, 28(3):111-119. DOI: 10.1684/ecn.2017.0399 [22] Ma QY,Huang DY,Zhang HJ, et al.Upregulation of bacterial-specific Th1 and Th17 responses that are enriched in CXCR5+CD4+ Tcells in non-small cell lung cancer[J]. Int Immunopharmacol,2017, 52:305-309. DOI: 10.1016/j.intimp.2017.09.024 [23] Ward-Hartstonge KA,Kemp RA.Regulatory T-cell heterogeneity and the cancer immune response[J]. Clin Transl Immunology,2017, 6(9): e154. DOI: 10.1038/cti.2017.43 [24] Dyck L,Wilk MM,Raverdeau M, et al.Anti-PD-1 inhibits Foxp3+ Treg cell conversion and unleashes intratumoural effector T cells thereby enhancing the efficacy of a cancer vaccine in a mouse model[J]. Cancer Immunol Immunother,2016, 65(12):1491-1498. DOI: 10.1007/s00262-016-1906-6 [25] Dong L, Zheng X, Wang K, et al.Programmed death 1/programmed cell death-ligand 1 pathway participates in gastric surgery-induced imbalance of T-helper 17/regulatory T cells in mice[J]. J Trauma Acute Care Surg, 2018, 85(3):549-559. DOI: 10.1097/TA.0000000000001903 [26] 张佳,张峰波,赵云娟, 等. 肺结核患者血清中 sPD-1和 sPD-L1与细胞因子的相关性研究[J].新疆医科大学学报, 2017, 40(2):131-135. DOI: 10.3969/j.issn.1009-5551.2017.02.001
2020, Vol. 36 
