The mRNA expression of TIPE2, Foxp3, and CTLA-4 in peripheral blood mononucleated cells in patients with chronic hepatitis C and their clinical significance

Kong Li; Jin Meng; Wang WeiZhen; Zhao SuXian; Wang ShanShan

doi:10.3969/j.issn.1001-5256.2019.02.016

Volume 35 Issue 2

Feb. 2019

Turn off MathJax

Article Contents

Abstract

References

Article Navigation > Journal of Clinical Hepatology > 2019 > 35(2): 323-327

PDF( 2049 KB)

The mRNA expression of TIPE2, Foxp3, and CTLA-4 in peripheral blood mononucleated cells in patients with chronic hepatitis C and their clinical significance

DOI: 10.3969/j.issn.1001-5256.2019.02.016

Department of Hepatology, Third Hospital of Hebei Medical University

Research funding:

Published Date: 2019-02-20

Abstract

Abstract

Objective To investigate the mRNA expression of tumor necrosis factor-alpha-induced protein 8-like 2 ( TIPE2) , Foxp3 ( a functional molecule for regulatory T cells) , and cytotoxic T-lymphocyte-associated antigen 4 ( CTLA-4) in peripheral blood mononuclear cells ( PBMCs) in patients with chronic hepatitis C ( CHC) and their clinical significance. Methods A total of 80 CHC patients who were hospitalized in The Third Hospital of Hebei Medical University from May 2012 to December 2016 and did not receive antiviral drugs or immunoregulatory drugs were enrolled as CHC group, and 45 healthy volunteers were enrolled as controls. Quantitative real-time PCR was used to measure the mRNA expression of TIPE2, Foxp3, and CTLA-4 in PBMCs; the correlation between liver biochemical parameters and HCV RNA was observed, as well as the influence of TIPE2 on Foxp3 and CTLA-4. The t-test was used for comparison of continuous data between two groups, the chi-square test was used for comparison of categorical data between two groups, and Pearson correlation was used for correlation analysis. Results Compared with the healthy control group, the CHC group had a significant reduction in the mRNA expression of TIPE2 ( 0. 564 ± 0. 232 vs 0. 704 ± 0. 165, t = 3. 569, P < 0. 001) and significant increases in the mRNA expression of Foxp3 ( 0. 701 ± 0. 405 vs 0. 527 ± 0. 184, t = 2. 725, P = 0. 007) and CTLA-4 ( 0. 638 ± 0. 211 vs 0. 448 ± 0. 134, t = 5. 449, P < 0. 001) . The mRNA expression of TIPE2 was negatively correlated with serum alanine aminotransferase ( r =-0. 368, P = 0. 001) , aspartate aminotransferase ( r =-0. 417, P < 0. 001) , total bilirubin ( r =-0. 416, P < 0. 001) , and HCV RNA load ( r =-0. 327, P = 0. 003) and was positively correlated with the mRNA expression of Foxp3 ( r = 0. 461, P < 0. 001) and CTLA-4 ( r = 0. 257, P = 0. 021) . The mRNA expression of Foxp3 was negatively correlated with total bilirubin ( r =-0. 284, P = 0. 011) . Conclusion CHC patients have abnormalities in the mRNA expression of TIPE2 and the mRNA expression and function of Foxp3 and CTLA-4, which is associated with the degree of hepatocellular injury and viral replication. The TIPE2 gene may be involved in the pathogenesis of CHC by positively regulating immune response mediated by regulatory T cells.
- hepatitis C, chronic,
- TIPE2,
- forkhead transcription factors,
- CTLA-4,
- peripheral blood mononuclear cell

FullText(HTML)

References(24)

References

[1]SUN H, GONG S, CARMODY RJ, et al.TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis[J].Cell, 2008, 133 (3) :415-426.

[2]KONG L, LIU K, ZHANG YZ, et al.Downregulation of TIPE2mRNA expression in peripheral blood mononuclear cells from patients with chronic hepatitis C[J].Hepatol Int, 2013, 7 (3) :844-849.

[3]SAKAGUCHI S, SAKAGUCHI N, ASANO M, et al.Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25) .Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases[J].J Immunol, 1995, 155 (3) :1151-1164.

[4]NAFADY A, NAFADY-HEGO H, ABDEWAHAB NM, et al.Peripheral lymphocytes analyses in children with chronic hepatitis Cvirus infection[J].Eur J Clin Invest, 2018, 48 (10) :e13004.

[5]EBINUMA H, NAKAMOTO N, LI Y, et al.Identification and in vitro expansion of functional antigen-specific CD25+Fox P3+regulatory T cells in hepatitis C virus infection[J].J Virol, 2008, 82 (10) :5043-5053.

[6]ZHAI N, LI H, SONG H, et al.Hepatitis C virus induces MD-SCs-like monocytes through TLR2/PI3K/AKT/STAT3 signaling[J].PLo S One, 2017, 12 (1) :e0170516.

[7]LUAN YY, YAO YM, ZHANG L, et al.Expression of tumor necrosis factor-αinduced protein 8 like-2 contributes to the immunosuppressive property of CD4+CD25+regulatory T cells in mice[J].Mol Immunol, 2011, 49 (1-2) :219-226.

[8]ZHANG L, SHI Y, WANG Y, et al.The unique expression profile of human TIPE2 suggests new functions beyond its role in immune regulation[J].Mol Immunol, 2011, 48 (9-10) :1209-1215.

[9]FONTENOT JD, GAVIN MA, RUDENSKY AY.Foxp3 programs the development and function of CD4+CD25+regulatory Tcells[J].Nat Immunol, 2003, 4 (4) :330-336.

[10]RUDENSKY AY.Regulatory T cells and Foxp3[J].Immunol Rev, 2011, 241 (1) :260-268.

[11]PASSERINI L, BACCHETTA R.Forkhead-box-P3 gene transfer in human CD4+T conventional cells for the generation of stable and efficient regulatory T Cells, suitable for immune modulatory therapy[J].Front Immunol, 2017, 8:1282.

[12]KITAGAWA Y, SAKAGUCHI S.Molecular control of regulatory T cell development and function[J].Curr Opin Immunol, 2017, 49:64-70.

[13]SMYK-PEARSON S, GOLDEN-MASON L, KLARQUIST J, et al.Functional suppression by FoxP3+CD4+CD25high regulatory T cells during acute hepatitis C virus infection[J].J Infect Dis, 2008, 197 (1) :46-57.

[14]GUO FB, WU JZ, AI LM, et al.Clinical significance of Th17/Treg and associated cytokines in peripheral blood in chronic hepatitis C patients with liver cirrhosis[J].J Clin Hepatol, 2017, 33 (3) :479-484. (in Chinese) 郭飞波, 武军驻, 艾黎明, 等.慢性丙型肝炎肝硬化患者外周血辅助性T淋巴细胞17/调节性T淋巴细胞及相关因子检测的临床意义[J].临床肝胆病杂志, 2017, 33 (3) :479-484.

[15]CLAASSEN MA, de KNEGT RJ, TILANUS HW, et al.Abundant numbers of regulatory T cells localize to the liver of chronic hepatitis C infected patients and limit the extent of fibrosis[J].J Hepatol, 2010, 52 (3) :315-321.

[16]ISHIBASHI M, YAMAGUCHI H, HIROTANI Y, et al.Contradictory intrahepatic immune responses activated in high-load hepatitis C virus livers compared with low-load livers[J].Arch Virol, 2018, 163 (4) :855-865.

[17]AMORAS EDA S, GOMES ST, FREITAS FB, et al.Intrahepatic mRNA expression of FAS, FASL, and FOXP3 genes is associated with the pathophysiology of chronic HCV infection[J].PLo S One, 2016, 11 (5) :e0156604.

[18]JIANG YY, ZHANG XH, ZHENG SJ.Change in immune status after antiviral therapy in patients with hepatitis C virus infection[J].J Clin Hepatol, 2018, 34 (2) :403-406. (in Chinese) 蒋莹莹, 张晓慧, 郑素军.HCV感染者抗病毒治疗前后免疫状态的变化[J].临床肝胆病杂志, 2018, 34 (2) :403-406.

[19]SHEVACH EM, DIPAOLO RA, ANDERSSON J, et al.The lifestyle of naturally occurring CD4+CD25+Foxp3+regulatory Tcells[J].Immunol Rev, 2006, 212:60-73.

[20]READ S, GREENWALD R, IZCUE A, et al.Blockade of CTLA-4on CD4+CD25+regulatory T cells abrogates their function in vivo[J].J Immunol, 2006, 177 (7) :4376-4383.

[21]LI BT, XIAO L.Research progress of the relationship between CTLA-4, CTLA-4 polymorphism and HCV infection[J/CD].Chin J Clinicians:Electronic Edition, 2013, 7 (23) :10905-10908. (in Chinese) 李邦涛, 肖丽.细胞毒性T淋巴细胞相关抗原4及其基因多态性在丙型病毒性肝炎中的研究进展[J/CD].中华临床医师杂志:电子版, 2013, 7 (23) :10905-10908.

[22]DOUMBA PP, SERTI E, BOUTSIKOU M, et al.Phenotypic and functional alterations of primary human PBMCs induced by HCV non-enveloped capsid-like particles uptake[J].Cell Mol Life Sci, 2013, 70 (18) :3463-3474.

[23]DING J, SU J, ZHANG L, et al.Crocetin activates Foxp3through TIPE2 in asthma-associated Treg cells[J].Cell Physiol Biochem, 2015, 37 (6) :2425-2433.

[24]FAN T, HUANG X, LIU C, et al.Egress of murine regulatory Tcells from the thymus requires TIPE2[J].Biochem Biophys Res Commun, 2018, 500 (2) :376-383.

Relative Articles

[1]	Zhao JinHua, Li JunFeng, Mao XiaoRong. Effect of T-lymphocyte phenotype on immune status in chronic hepatitis B virus infection and its application value[J]. Journal of Clinical Hepatology, 2020, 36(5): 1019-1023. doi: 10.3969/j.issn.1001-5256.2020.05.014
[2]	Chen Bin, Zhang Tao, Zhu WenFang, Peng Jie, Zhang QianQian, Li YunFang, Ding XiuLi. Effect of the warming and heat-clearing method on the percentage of regulatory T lymphocytes/T helper 17 cells in rats with acute-on-chronic liver failure[J]. Journal of Clinical Hepatology, 2018, 34(12): 2642-2647. doi: 10.3969/j.issn.1001-5256.2018.12.026
[3]	Gao WeiHua, Ge KuanXue, Xiang XiaoXing. Association of Th17 cells, regulatory T cells, and their imbalance with nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2018, 34(6): 1347-1350. doi: 10.3969/j.issn.1001-5256.2018.06.046
[4]	Wang Yan, Huang YouYing, Ma Yan, Guo Feng, Wang XiaoBo, Wang XiaoZhong. Expression features of follicular helper T cells in peripheral blood in patients with chronic hepatitis B[J]. Journal of Clinical Hepatology, 2018, 34(1): 58-62. doi: 10.3969/j.issn.1001-5256.2018.01.012
[5]	Ge KuanXue, Gao WeiHua, Xiang XiaoXing. Association of regulatory T cells, T helper 17 cells, and change in their balance with autoimmune hepatitis[J]. Journal of Clinical Hepatology, 2018, 34(7): 1573-1576. doi: 10.3969/j.issn.1001-5256.2018.07.045
[6]	Li JianYun, Tu ChuanQing, He De, Wang DianWen, Huang Can, Zhang XuYan, Feng Chun. Clinical significance of measurement of T lymphocyte subsets before splenectomy in patients with primary immune thrombocytopenia[J]. Journal of Clinical Hepatology, 2017, 33(1): 150-154. doi: 10.3969/j.issn.1001-5256.2017.01.033
[7]	He JunNan, Zhao ShouSong. Research advances in association between regulatory T cells and hepatitis B virus infection[J]. Journal of Clinical Hepatology, 2016, 32(2): 361-365. doi: 10.3969/j.issn.1001-5256.2016.02.036
[8]	Zhang FeiFei, Chen Hui, Lyu Jun. Role of T-helper cell 17 in the development and progression of hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2016, 32(8): 1626-1629. doi: 10.3969/j.issn.1001-5256.2016.08.046
[9]	Ji LongShan, Sun XueHua, Zhou ZhenHua, Zhang Xin, Gao YaTing, Gao YueQiu, Li Man. Role of follicular helper T cells in development and progression of liver diseases[J]. Journal of Clinical Hepatology, 2016, 32(6): 1230-1234. doi: 10.3969/j.issn.1001-5256.2016.06.050
[10]	Zhou Yan, Jing Xiang, Zhu ZhengYan. Roles of regulatory T cells and T-helper cells in hepatitis B virus-related liver diseases[J]. Journal of Clinical Hepatology, 2016, 32(10): 1994-1997. doi: 10.3969/j.issn.1001-5256.2016.10.040
[11]	Li CaiDong, Chen XiLian, Duan ZhengJun, Liu XueMei, Wu Bin. Determination of proportions of T cell subsets and levels of interleukin-15 and interleukin-16 in peripheral blood of patients with chronic hepatitis B virus infection and correlation between them[J]. Journal of Clinical Hepatology, 2015, 31(11): 1857-1861. doi: 10.3969/j.issn.1001-5256.2015.11.021
[12]	Shi GuangYing, Ma XiaoYuan, Xie JingDong. Changes in T lymphocyte subsets and cytokines in peripheral blood of patients with primary biliary cirrhosis after treatment with different doses of ursodeoxycholic acid[J]. Journal of Clinical Hepatology, 2015, 31(9): 1447-1451. doi: 10.3969/j.issn.1001-5256.2015.09.020
[13]	Li CaiDong, Chen XiLian, Tian PengFei, Li HuiJun, Wu Bin. Correlation analysis of percentages of T lymphocyte subsets and CD4~+CD25~+ regulatory T cells and HBV DNA level in peripheral blood of chronic hepatitis B patients[J]. Journal of Clinical Hepatology, 2015, 31(4): 541-545. doi: 10.3969/j.issn.1001-5256.2015.04.016
[14]	Wang Yu, Ma ZhiYuan, Guo YongHong, He Yu, Zhang Ying, Xie YuMei, Ma Li, Zhou Yun, Jia ZhanSheng. Investigation of CD4+CXCR5+ follicular helper T cell frequency and expression of related functional molecules in peripheral blood of hepatitis C virus patients[J]. Journal of Clinical Hepatology, 2013, 29(5): 379-382.
[15]	Ding QiaoYun, Yu HaiYing, Sun WeiWei, Pan Jian, Cao XingGuo, Wang Lei. The changes of peripheral blood T-lymphocyte subsets in pediatric severe hepatitis[J]. Journal of Clinical Hepatology, 2011, 27(7): 729-730.

Supplements(0)

Cited By

Cited by

Periodical cited type(8)

1.	蒋丽莎，马洪升. 日归手术——中国日间手术的升华. 华西医学. 2022(02): 161-164 .
2.	雷甜甜，梁鹏，马洪升，蒋丽莎. 四川大学华西医院日归手术管理实践. 广东医学. 2022(10): 1222-1228 .
3.	方宁波，陈伟力. 腹腔镜胆囊切除术日间手术围术期指标观察及患者延迟出院原因分析. 江西医药. 2022(10): 1524-1527 .
4.	刘力玮，郑亚民，刘东斌，王悦华，刘家峰，梁阔，江华，高崇崇，于志浩，徐大华. 日间腹腔镜胆囊切除术的可行性分析. 腹腔镜外科杂志. 2021(05): 359-362 .
5.	杨奕夫，黎柏峰，肖艳. 日间腹腔镜胆囊切除术质量控制的研究进展. 腹腔镜外科杂志. 2020(10): 796-798+800 .
6.	李航，赵礼金. 老年患者腹腔镜胆囊切除日间手术的安全性分析. 中国普通外科杂志. 2019(08): 1012-1017 .
7.	石鑫，秦琦瑜，刘维丽，胥静，王威. “三镜”联合治疗胆囊结石合并肝外胆管结石手术效果及安全性研究. 临床军医杂志. 2018(06): 710-712 .
8.	张少成，张亚辉，徐小梦. 年龄因素对上胆道疾病患者行腹腔镜胆囊切除术安全性的影响. 深圳中西医结合杂志. 2018(06): 184-186 .

Other cited types(1)

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Get Citation

PDF

XML

Article Metrics

Article views (1859) PDF downloads(295)

The mRNA expression of TIPE2, Foxp3, and CTLA-4 in peripheral blood mononucleated cells in patients with chronic hepatitis C and their clinical significance

DOI: 10.3969/j.issn.1001-5256.2019.02.016