Presenting Author: Hsiu-Jung Liao
, Researcher at Far Eastern Mem. Hosp.
Abstract:
Chronic hepatitis B virus (HBV) infection results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The liver is an immune tolerance organ; the immune-suppressive tissue microenvironment limits the immune response and may facilitate persistent infection by HBV. This study investigated the expression of immunity-related factors in the liver microenvironment in response to HBV. We identified Interleukin 27 (IL-27) is induced by HBV in the liver microenvironment, and its expression is associated with HBV persistence. We identified that IL-27 gene expression was strongly induced in the liver microenvironment by HBV in RNA-Seq analysis. The elevation of IL-27 was highly correlated with HBV viral persistence and is associated with CD8 dysfunction with impaired production and enhanced expression of PD-1 and Tim-3 in liver infiltrating CD8 T cells. In addition, the core null HBV mutant induced significantly higher IL-27 expression in the liver microenvironment and enhanced viral persistence. The IL-27 was produced by the liver macrophage-linage cells, and depletion with clodronate significantly reduced the production of IL-27 in the liver. Moreover, mice with IL-27 deficiency result in enhanced clearance of HBV and reversed CD8 T cell dysfunction. Collectively, we reveal that HBV induces IL-27 in the liver microenvironment and enhances viral persistence and T-cell dysfunction. Thus, it suggests that IL-27 represents a promising therapeutic target for HBV infection.
IL-27 is induced in liver microenvironment by hepatitis B virus and enhances viral persistence
Category
Poster and Podium (Block Symposium)
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Date: May 5 Presentation Time: 03:15 PM to 04:30 PM Room: Exhibit Hall F1