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Intrahepatic Expression of Programmed Death-1 and its Ligands in Patients with HBV-Related Acute-on-Chronic Liver Failure

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Abstract

Hepatitis B virus (HBV) infection is a major public health problem, and HBV-related acute-on-chronic liver failure (HBV-ACLF) has an extremely poor prognosis due to a lack of understanding of pathogenesis as well as a lack of effective treatments. Signals from the inhibitory receptor programmed death-1 (PD-1) have been demonstrated to be involved in regulating the pathogenesis of infectious diseases. However, the expression of PD-1 and its ligands in HBV-ACLF patients has yet to be evaluated. In this study, the expression of PD-1 and its ligands, PD-L1 and PD-L2, in liver biopsies from HBV-ACLF as well as chronic hepatitis B (CHB) patients were analyzed by immunohistochemistry. The results showed that all three molecules were observed in the HBV-ACLF samples and their levels were significantly higher than they were in CHB. Immunofluorescence double-staining showed that PD-1 was found on CD3+, CD8+ T cells, CD56+ NK cells, CD68+ macrophages, CK-18+ epithelial cells, and CD16+ monocytes. The PD-L1 expression was observed on all cell types detected and the PD-L2 was chiefly on CK-18+ epithelial cells and CD31+ endothelial cells. Interestingly, high levels of virus-induced procoagulant molecule fibrinogen-like protein 2 (FGL2) were observed in liver sections from HBV-ACLF, and PD-L1 and PD-L2 expression was also observed on FGL2+ cells in these patients. Our combined results suggest that the expression of PD-L1 and PD-L2 may be biomarkers to identify and diagnose ACLF, and a clear understanding of their functional roles should further elucidate the pathogenesis of this disease.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (NSFC No. 81171585, 30872374 and 61141012).

Competing interests

None of the authors have any conflicts of interest related to this manuscript.

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Authors and Affiliations

  1. Institute of Immunology, PLA, Third Military Medical University, Chongqing, 400038, People’s Republic of China

    Dayan Cao, Huan Xu, Lei Fei, Zhunyi Xie, Yuzhang Wu & Yongwen Chen

  2. Undergraduate Administration Office, Third Military Medical University, Chongqing, 400037, People’s Republic of China

    Dayan Cao & Huan Xu

  3. Department of Emergency, South-West Hospital, PLA, Third Military Medical University, Chongqing, 400037, People’s Republic of China

    Guoning Guo

  4. Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400039, People’s Republic of China

    Zhihua Ruan

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  1. Dayan Cao
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Correspondence to Yongwen Chen.

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Dayan Cao and Huan Xu are equally to this work.

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Cao, D., Xu, H., Guo, G. et al. Intrahepatic Expression of Programmed Death-1 and its Ligands in Patients with HBV-Related Acute-on-Chronic Liver Failure. Inflammation 36, 110–120 (2013). https://doi.org/10.1007/s10753-012-9525-7

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