标题:Prostaglandin E2 facilitates Hepatitis B virus replication by impairing CTL function
作者:Li, Xiaoyan; Xie, Tingting; Gao, Lifen; Ma, Chunhong; Yang, Xiaoyun; Liang, Xiaohong
作者机构:[Li, Xiaoyan; Xie, Tingting; Gao, Lifen; Ma, Chunhong; Liang, Xiaohong] Shandong Univ, Sch Med, Key Lab Expt Teratol, Minist Educ,Key Lab Infect & Imm 更多
通讯作者:Liang, XH;Yang, XY
通讯作者地址:[Liang, XH]44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China;[Yang, XY]107 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.
来源:MOLECULAR IMMUNOLOGY
出版年:2018
卷:103
页码:243-250
DOI:10.1016/j.molimm.2018.08.009
关键词:PGE2; Chronic HBV infection; CD8+T cells; Cytotoxicity; Cytokine; secretion
摘要:Reversal of T cell dysfunction is a novel and promising approach for the treatment of chronic diseases. PGE2, one of most studied Prostaglandins, exhibits strong and versatile immunoregulation activity on different immune cells including T cells, and has become a promising therapeutic target. Here we found that compared to healthy donors, patients with chronic Hepatitis B virus (HBV) infection had significantly elevated serum PGE2 level. Importantly, serum PGE2 concentration correlated with viral load and liver damage in Chronic hepatitis B(CHB) patients. In AAV-HBV1.2 mouse model, administration of PGE2 analogue promoted HBV replication, while antagonists for EP2 and EP4, two important receptors for PGE2, inhibited virus replication. However, PGE2 analogue had no significant effect on the growth and virus replication in cultured HBV-harboring hepatocyte cell line. Further analysis showed that high PGE2 level in CHB patients correlated with high Tim-3 expression and low level of perforin and granzme B in CD8 + T cells. In parallel, blockade of PGE2 signaling restored the function of CD8 + T cells and controls HBV infection. Depletion of CD8 + T cells almost abrogated the effects of PGE2 on HBV replication. These findings identify PGE2 as a negative regulator for CD8 + T cells contributing to HBV persistence and the intervention of PGE2 signaling might be of potentially translational significance.
收录类别:SCIE
资源类型:期刊论文
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