Clinical Significance and Properties of IFN-gamma+IL-17(+) Th17 Cells in Liver Injury Associated with Chronic Hepatitis B Virus Infection

作者全名："Xie, Hao; Zeng, Jingyan; Yan, Xiong; Shen, Na; Zheng, Xiao; Luo, Hongchun"

作者地址："[Xie, Hao; Zeng, Jingyan; Zheng, Xiao; Luo, Hongchun] Chongqing Med Univ, Dept Infect Dis, Affiliated Hosp 1, Chongqing, Peoples R China; [Yan, Xiong] Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Chongqing, Peoples R China; [Shen, Na] Chongqing Med Univ, Dept Emergency, Affiliated Hosp 1, Chongqing, Peoples R China"

通信作者："Luo, HC (通讯作者)，Chongqing Med Univ, Dept Infect Dis, Affiliated Hosp 1, Chongqing, Peoples R China."

来源：DIGESTION

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000877189600001

JCR分区：Q3

影响因子：3.2

年份：2022

卷号：103

期号：6

开始页：438

结束页：450

文献类型：Article

关键词：Acute-on-chronic liver failure; CCR5; CXCR3; IFN-gamma+IL-17+Th17 cells; Regulatory Th cells

摘要："Introduction: Our previous study demonstrated that intrahepatic Th17 cells exacerbated the progression of chronic hepatitis B virus (HBV) infection. Meanwhile, we found a small group of IFN-gamma and IL-17 double-positive Th17 cells (IFN-gamma+IL-17(+) Th17 cells) in liver tissues. This study aimed to investigate the clinical significance and properties of IFN-gamma+IL-17(+) Th17 cells in liver injury associated with chronic HBV infection. Methods: The frequencies of CD4(+) Th cells, Tregs, and CD4(+) T cells expressing specific chemokine receptors in the blood and liver tissues were detected using flow cytometry. The chemotaxis of C C chemokine receptor 5 (CCR5) and C-X-C chemokine receptor 3 (CXCR3) toward IFN-gamma+IL-17(+) Th17 cells and Tregs was evaluated by transwell chemotactic assay. Analyses of different variables were performed using GraphPad Prism v 5.01 and IBM SPSS Statistics 23.0. HBV-specific IFN-gamma+IL-17(+) Th17 cells were investigated using a cell stimulation assay with HBV antigens in vitro. Results: The frequencies of IFN-gamma+IL-17(+) Th17, Th17 cells, and Tregs in the blood were increased from normal controls to chronic hepatitis B (CHB) and acute-on-chronic liver failure (ACLF). The same trend could also be observed in CHB liver tissues compared to those in CHB blood specimens. Furthermore, the frequencies of IFN-gamma+IL-17(+) Th17 cells were positively associated with Th17 cells, Th17 cell-related cytokines (IL-17 and IL-6), HBV DNA load, and the levels of HBsAg, HBeAg, and ALT. The ratios of IFN-gamma+IL-17(+) Th17 cells to Tregs extremely decreased in ACLF blood specimens compared with those in CHB blood specimens. Additionally, CCR5 and CXCR3 were conducive to the recruitment of IFN-gamma+IL-17(+) Th17 cells and Tregs to liver tissue. Conclusions: IFN-gamma+IL-17(+) Th17 cells have Th17 cell-like properties in the progression of chronic HBV infection. CCR5 and CXCR3 facilitated the recruitment of IFN-gamma+IL-17(+) Th17 cells and Tregs to the liver. Importantly, the ratio of IFN-gamma+IL-17(+) Th17 cells to Tregs might be an effective assessment indicator of the severity of liver injury."

基金机构："National Natural Science Foundation of China [81502117]; Natural Science Foundation of Chongqing, China [cstc2021jcyjmsxmX0202]; Medical Research Foundation of Chongqing Health Committee [2020MSXM099]"

基金资助正文："Grant support: this study was supported by the National Natural Science Foundation of China (Grant No. 81502117), Natural Science Foundation of Chongqing, China (Grant No. cstc2021jcyjmsxmX0202), and the Medical Research Foundation of Chongqing Health Committee (Grant No. 2020MSXM099)."