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肝胆相照论坛 论坛 学术讨论& HBV English 前列腺素E2通过损害CTL功能促进乙型肝炎病毒复制。 ...
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前列腺素E2通过损害CTL功能促进乙型肝炎病毒复制。 [复制链接]

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才高八斗

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发表于 2018-10-17 09:11 |只看该作者 |倒序浏览 |打印
Mol Immunol. 2018 Oct 12;103:243-250. doi: 10.1016/j.molimm.2018.08.009. [Epub ahead of print]
Prostaglandin E2 facilitates Hepatitis B virus replication by impairing CTL function.
Li X1, Xie T2, Gao L2, Ma C2, Yang X3, Liang X4.
Author information

1
    Key Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, 250012, China; Department of laboratory, Baoding NO.1 Central hospital, Baoding, Hebei, 071000, China.
2
    Key Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, 250012, China.
3
    Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China. Electronic address: [email protected].
4
    Key Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, 250012, China. Electronic address: [email protected].

Abstract

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.
KEYWORDS:

CD8+ T cells; Chronic HBV infection; Cytokine secretion; Cytotoxicity; PGE2

PMID:
    30321734
DOI:
    10.1016/j.molimm.2018.08.009

Rank: 8Rank: 8

现金
62111 元 
精华
26 
帖子
30437 
注册时间
2009-10-5 
最后登录
2022-12-28 

才高八斗

2
发表于 2018-10-17 09:12 |只看该作者
Mol Immunol。 2018年10月12日; 103:243-250。 doi:10.1016 / j.molimm.2018.08.009。 [提前打印]
前列腺素E2通过损害CTL功能促进乙型肝炎病毒复制。
李X1,谢T2,高二,马C2,杨X3,梁X4。
作者信息

1
    山东大学医学院山东省感染与免疫重点实验室,免疫学教育部重点实验室,山东济南250012;保定市第一中心医院实验室,河北保定071000
2
    山东大学医学院山东省感染与免疫重点实验室,免疫学教育部重点实验室,山东济南250012
3
    山东大学齐鲁医院消化内科,山东济南250012电子地址:[email protected]
4
    山东大学医学院山东省感染与免疫重点实验室,免疫学教育部重点实验室,山东济南250012电子地址:[email protected]

抽象

逆转T细胞功能障碍是治疗慢性疾病的一种新颖且有前途的方法。 PGE2是研究最多的前列腺素之一,在包括T细胞在内的不同免疫细胞上表现出强大且通用的免疫调节活性,并已成为一种有前景的治疗靶点。在这里,我们发现与健康供体相比,慢性乙型肝炎病毒(HBV)感染患者的血清PGE2水平显着升高。重要的是,血清PGE2浓度与慢性乙型肝炎(CHB)患者的病毒载量和肝损伤相关。在AAV-HBV1.2小鼠模型中,施用PGE2类似物促进HBV复制,而EP2和EP4的拮抗剂(PGE2的两种重要受体)抑制病毒复制。然而,PGE2类似物对培养的携带HBV的肝细胞系中的生长和病毒复制没有显着影响。进一步分析显示,CHB患者的高PGE2水平与CD8 + T细胞中高Tim-3表达和低水平的穿孔素和颗粒B相关。同时,阻断PGE2信号传导恢复了CD8 + T细胞的功能并控制了HBV感染。 CD8 + T细胞的消耗几乎消除了PGE2对HBV复制的影响。这些发现将PGE2鉴定为导致HBV持续性的CD8 + T细胞的负调节因子,并且PGE2信号传导的干预可能具有潜在的翻译意义。
关键词:

CD8 + T细胞;慢性HBV感染;细胞因子分泌;细胞毒性; PGE2

结论:
    30321734
DOI:
    10.1016 / j.molimm.2018.08.009
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