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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
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